43
Hormonal Carcinogenesis III
Hormonal Carcinogenesis III
Springer New York Berlin Heidelberg Barcelona Hong Kong London Milan Paris Singapore Tokyo
Jonathan 1. Li, Ph.D. Professor of Phannacology, Toxicology, and Therapeutics Director, Division of Etiology and Prevention of Hormonal Cancers Hormonal Carcinogenesis Laboratory, University of Kansas Cancer Center
Sara Antonia Li, Ph.D. Associate Professor of Phannacology, Toxicology, and Therapeutics Division of Etiology and Prevention of Hormonal Cancers Hormonal Carcinogenesis Laboratory, University of Kansas Cancer Center
Janet R. Daling, Ph.D. Division of Public Health Sciences Fred Hutchinson Cancer Research Center University of Washington Editors
Hormonal Carcinogenesis III Proceedings of the Third International Symposium
With 147 Illustrations
, Springer
Jonathan 1. Li, Ph.D. Professor of Pharmacology,
Toxicology, and Therapeutics Director, Division of Etiology &
Prevention of Hormonal Cancers Kansas Cancer Institute University of Kansas Medical Center Kansas City, Kansas 66160 USA
Janet R. Daling, Ph.D Division of Public Health Sciences Fred Hutchinson Cancer Research Center University of Washington Seattle, Washington 98101 USA
Library of Congress Cataloging-in-Publication Data
Sara Antonia Li, Ph.D. Associate Professor of Pharmacology,
Toxicology, and Therapeutics Division of Etiology &
Prevention of Hormonal Cancers Kansas Cancer Institute University of Kansas Medical Center Kansas City, Kansas 66160 USA
Honnonal carcinogenesis m : proceedings of the third international symposium I editors. Jonathan J. Li. Sara Antonia Li, Janet R. Daling.
p.;cm. Includes bibliographical references and index. ISBN-13:978-1-4612-7411-7 e-ISBN-13:978-1-4612-2092-3 001: 10.1007/978-1-4612-2092-3
1. Generative organs-Cancer-Congresses. 2. Breast-Cancer-Etiology-Congresses. 3. Honnones. Sex-Carcinogenicity-Congresses. 4. Cancer-Endocrine aspects-Congresses. I. Title: Honnonal carcinogenesis 3. II. Title: Honnonal carcinogenesis three. m. Li, Jonathan J. IV. Li. Sara Antonia. V. Daling. Janet R. VI. International Symposium on Honnonal Carcinogenesis (3rd : 1998 : Seattle, Wash.)
[DNLM: 1. Neoplasms, Honnone-Dependent-Congresses. 2. Breast NeopJasms-etioJogy-Congresses. 3. Neoplastic Processes-Congresses. 4. Prostate Neoplasms-etioJogy-Congresses. 5. Receptors, Cell Surface-physiology-Congresses. 6. Sex Honnones-adverse effects-Congresses. QZ 200 H8113 2001] RC280.G4 H67 2001 616.99'4071-dc21 00-058849
Printed on acid-free paper. © 2001 Springer-Verlag New York, Inc. Softcover reprint of the hardcover 1st edition 200 1
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Springer-Verlag New York Berlin Heidelberg A member uf BenelsmonnSpringer Science+Business Media GmbH
The real voyage of discovery consists not in seeking new landscapes but in having new eyes.
- Marcel Proust
Christopher and Stephanie - Jonathan J. Li - Sara Antonia Li
Lane - Janet R. Dating
Acknowledgments
Patrons
Fred Hutchinson Cancer Research Center National Cancer Institute
Division of Cancer Biology Division of Cancer Control & Population Sciences
Wyeth-Ayerst Research National Institute of Environmental Health Sciences
National Institute of Environmental Health Sciences -International Programs
Sponsors
National Institute of Child Health & Human Development Office of Research on Women's Health
Hoechst Marion Roussel Seattle Breast Cancer Research Program
Contributors
Alza Corporation National Institute of Diabetes & Digestive & Kidney Diseases
Nitta Gelatin Inc. The Council for Tobacco Research
Amgen DAKO
Par
tici
pant
s of
the
Thi
rd I
nter
nati
onal
Hor
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al C
arci
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s Sy
mpo
sium
Executive and Scientific Advisory Boards (EB, SAB) and Consultants (C)
Top Row, L to R: J. Rosen (SAB), J. Pickar (SAB), E. Jensen (SAB), A. LlombartBosch (SAB) Bottom Row, L to R: J.J. Li (EB), H. Rochefort (SAB), G. Mueller (C), S. Nandi (C), J. Daling (EB), S.A. Li (EB), S. Liao (SAB)
SAB members not present: P. Chambon, G. Colditz, S. 1. Collins, M. Gallo, 1.A. Gustafsson, L. Hartwell, H.C. Pitot, R. Sutherland, F. Waldman
Preface
Since our previous symposium in 1995, the pace of research in hormones and cancer has accelerated. Progress in our understanding of hormonal carcinogenic processes has been a direct result of the advances made in cell biology, endocrinology, and carcinogenesis at the molecular level. The newer fields of molecular genetics and cytogenetics already have and are expected to continue to playa major role in furthering our understanding of the cellular and molecular events in hormonal carcinogenesis.
It has become increasingly clear that the risk of naturally occurring sex hormones in carcinogenic processes, both in human and in animal models, requires only minute quantities of hormones, at both the serum and tissue levels. Moreover, hormone target tissues for neoplastic transformation, perhaps with the exception of the liver, generally have relatively modest ability to metabolize sex hormones, such as the breast and prostate.
Table 1 summarizes the serum, and in most cases, the tissue levels of sex hormones, both endogenously and exogenously ingested, which are associated with increased risk for endocrine-associated cancers such as breast, endometrium, and prostate, as well as the hormone levels of four experimental models that have been shown to elicit high tumor incidences. In contrast to the human, in which the hormone levels are cyclic, however, the latter require continuous hormone exposure at these relatively low levels.
Although likely multi-factorial, it is increasingly evident that estrogens and perhaps to a lesser extent progestins are critical etiologic agents in breast cancer development. While the association of estrogens has been well established for endometrial cancer, it was not until after 1990 that endogenous estrogen levels have been associated with increased breast cancer risk. These studies, drawn from larger case-control studies, many of them nested within prospective cohorts, have now firmly established this association. Moreover, European and American studies such as the Nurse's Health Study, have also shown that both ERT and HRT ingestion also increases breast cancer risk. In regard to prostate cancer, there is substantial evidence, both from human and animal studies, that androgens are essential during the initiation and promotion stages of this neoplasm. In all of these endocrine-associated cancers, much needs to be known concerning the precise role of these hormones in neoplastic processes. This remains the primary subject of these symposia.
ix
x Preface
Table 1. Normal serum, breast and endometrial tissue levels and those required for experimental hormonal carcinogenesis
Hormone
Testosterone
+ Testosterone
Species
Human, fj! Cycling ERT Post-Meno
Human, r!
Hamster, fj! Cycling H. impl.s r!
Rat,ACI, fj! Cycling H. impl.s
Rat, Noble,r! H. impl.s
Mouse, r! transgenic
Serum (nglml)
0.02 - 0.36 (1)
2.5 (2)
30 - 110 (1)
0.06-0.36 (4) 2.5 (4)
0.04-0.12 (5) 0.18-0.21 (5)
~ 0.04 (6)
2.3 (6)
0.006 (7)
Organ
Breast & Endometrium
Prostate
Kidney Kidney
MamGland
Prostate
Testes
Tissue (pglmg P)
114 (8)
95 (8)
5.7-12.3 3.9-5.5
2 ND. not detennined 3 pglg tissue 4 mglg tissue ~ Honnone(s) implanted
1. Schiff!, Walsh B (1995) Menopause. In: Becker KL (ed) Principles and Practice of Endocrinology and Metabolism, 2nd Edition. J.B. Lippinicott Co, New York, pp.916.
2. Mistry JS, Ranadive G, Saujahl G et al (1997) Estrone sulfate as a marker of estrogenicity in women. Proc. Endocrine Soc 79:P3-418.
3. Hankinson SE, Manson JE, Spiegelman D et al (1995) Reproducibility of plasia hormone levels in postmenopausal women over a 2-3-year period. Cancer Epidemiol Biomarkers Prevent 4:649-654.
4. Li SA, Xue Y, Xie Q et al (1994) Serum and tissue levels of estradiol during estrogen-induced renal tumorigenesis in the Syrian hamster. J Steroid Biochem Molec Bioi 48:283-286.
Preface xi
5. Shull JD, Spady TJ, Snyder MC et al (1997) Ovary-intact, but not ovariectomized female ACI rats treated with 17p-estradiol rapidly develop mammary carcinoma. Carcinogenesis 18:1595-1601.
6. Leav I, Ho SM, Ofren P et al (1988) Biochemical alternatives in sex hormoneinduced hyperplasia and dysplasia of the dorsolateral prostate of Noble rats. J Nat Cancer Inst 80: 1045-1053.
7. Fowler KA, Gill K, Kirma N et al (1999) Overexpression of aromatase leads to development of testicular Leydig cell tumors: An in-vivo model for hormonemediated testicular cancer. Am J Path (in press).
8. Thussen JHH, Van Landeghem, Poortman J (1996) In: Ann NY Acad Sci. Angeli A, Bradlow HL, Dogiotti L (eds) Volume 464. New York, pp. 106-116.
Once again, we would like to express our deep gratitude to the members of the Scientific and Advisory Boards for their time and effort in assisting us in selecting speakers which provided a truly outstanding, cohesive program. The editors are grateful to Drs. M. Aldaz, J. Daling, S. Liao, G. Mueller, S. Nandi, J.S. Norris, C. Walker, and F. Waldman for their assistance in critically reviewing the manuscripts presented herein. We again are deeply indebted to Dr. J.H. Pickar, Wyeth Ayerst, and G.A. Lucier, NIEHS, for their continuous generous support of these symposia. We thank Dr. L. Hartwell and the WeisslDaling staff at the Fred Hutchinson Cancer Center for providing the fine facilities, technical support, and both time and effort on behalf of this symposium. Special thanks to Ms. Carolyn Bums for unstinting help in keeping this symposium on course. We are indebted to Ms. Stephanie Parks for her dedication and gracious equanimity during all stages of this symposium. We are grateful to Ms. Tandria Price for her excellent assistance in bringing this volume to the accustom high standard expected. We are also very grateful to the organizations listed separately for their contributions to this symposium, without their help this meeting could not have taken place.
Kansas City, Kansas
Seattle, Washington
Jonathan J. Li, Ph.D. Sara Antonia Li, Ph.D.
Janet Daling, Ph.D.
Contents
Dedication ............................................ v
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vi
Preface..... .......... . ...... . ....... ....... . . . ....... ix
Participants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxi
Contributors .......................................... xxix
Symposium Address Hormonal Carcinogenesis: Perceptions, Challenges, and Anticipations Gerald C. Mueller. ........................... 1
STATE OF THE ART LECTURES •••.•.•.•••• 23
1
2
3
The Numbers Game with Estrogen Receptors and Growth Regulation Jack Gorski, Tae-Yon Chun, and Douglas Wendell
Expression Genetics of Hormone Dependent Human Tumors Arthur B. Pardee, Heide L. Ford, Debajit K. Biswas, Katherine J. Martin, and Ruth Sager ................. .
New Directions in Epidemiologic Studies of Hormonally-related Cancers Janet R. Daling, Kathleen E. Malone, Elaine A. Ostrander, and Peggy L. Porter .............................. .
xii
25
37
44
Contents xiii
PART 1. EPIDEMIOLOGY: BREAST AND PROSTATE CANCER.......... 59
4
5
6
Estrogen Causes Breast Cancer: Increasing Duration of Use of Postmenopausal Hormones Increases the Risk of Breast Cancer Graham A. Colditz ........................ .
Frequency of BRCA2 Mutations in Women with Early Onset Breast Cancer Drawn from a Population-Based Study Kathleen E. Malone, Janet R. Daling, Nicola M. Suter, Kara Cushing, Thora Jonnasdottir, and Elaine A. Ostrander . . . . . . . . . . . . . . . . . . . . . . . . .
Prostate Cancer, Androgens, and Estrogens Janet L. Stanford . . . . ...................... .
PART 2. MOLECULAR GENETICS OF
61
70
87
HORMONAL CANCERS. . . . . . . . . . . . . . . . . . . . . 97
Introduction Breast Cancer Molecular Cytogenetics Frederic M. WaIdman . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
7
8
Genome Scanning and Tissue Microarrays for the Analysis of Molecular Mechanisms Underlying Hormone Therapy Failure in Prostate Cancer Lukas Bubendorf and Olli-P KaIlioniemi ............. .
Serial Analysis of Gene Expression in Breast Cancer Cells C. Marcelo Aldaz, Andrzej Bednarek, April Charpentier, Michael MacLeod, Kathleen Hawkins, and Kendra Laflin
9 The Effects of Triphenylethylene Antiestrogens on Parameter of Multistage Hepatocarcinogenesis in the Rat Yvonne P. Dragan, Emile Nuwaysir, Linda Sargent,
103
113
Dong-hui Li,V. Craig Jordan, and Henry C. Pitot . . . . . . . . 124
xiv Contents
PART 3. ESTROGEN RECEPTOR INTERACTIONS .................................. 137
Introduction The Curious Pharmacology of the Antiestrogens Elwood V. Jensen ................................ 139
10
11
Estrogen Receptor~: An Important Player in Estrogen Action Jan-Ake Gustafsson .............................. .
Estrogen Receptor Mediated Genomic Instability in the Syrian Hamster Kidney: A Critical Event in Hormonal Oncogenesis Jonathan J. Li, S. John Weroha, Marilyn Cansler, and Sara Antonia Li ................................. .
PART 4. ESTROGENIPROGESTERONE -
144
149
BREAST CANCER ................................ 159
Introduction Breast Cancer Prevention with Estrogen and Progesterone: Mimicking the Protective Effect of Pregnancy Satyabrata Nandi, Raphael C. Guzman, Jason Yang, Lakshmanaswamy Rajkumar, and Gudmundur Thordarson 161
12
13
14
The Dual Role of Estrogens and Cathepsin D in Invasion and Metastasis Henri Rochefort ................................ .
Estrogen-induced Breast Cancer in Female ACI Rats Sara Antonia Li, Joshua DeZhong Liao, and Jonathan J. Li ................................ .. .
A Transgenic Mouse Model for Mammary Carcinogenesis Kristen L. Murphey and Jeffrey M. Rosen ............ .
166
178
189
Contents xv
PART 5. CELL CYCLE, CELL PROLIFERATION ................................ 199
Introduction Receptor Tyrosine Kinases and the Effects of Ovarian Steroids on Cell Proliferation Richard P. DiAugustine, Diane M. Klotz, and R. Gregg Richards ............................ 201
15
16
Transcriptional Control of Cell Cycle Progression by Estrogenic Hormones: Regulation of Human Cyclin D1 Gene Promoter Activity by ER-« Valeria Belsito Petrizzi, Luigi Cicatiello, Lucia Altucci, Raffaele Addeo, Raphaelle Borgo, Massimo Cancemi, Massimo Ancora, Juan Leyva, Francesco Bresciani, and Alessandro Weisz ............................... .
Estrogen Regulation of Cell Cycle Progression Owen W.J. Prall, Eileen M. Rogan, Elizabeth A. Musgrove, Colin K.W. Watts, and Robert L. Sutherland .......... .
PART 6. ONCOGENESrrUMOR
206
220
SUPPRESSOR GENES.. .......................... 229
17
18
19
Estrogen and c-myc Protooncogene Actions in Human Breast Cancer Robert P.e. Shiu, D. Dubik, M. Venditti, J. Sparling, B. Iwasiow, and Peter H. Watson ................... .
Steroid Hormone Regulation of Vascular Endothelial Growth Factor (VEGF) Production: A Potential Step in Hormonal Carcinogenesis Salman M. Hyder, Holly L. Boettger-Tong, Sari MiikeHi, and George M. Stancel ........................... .
TGF -plEstrogen-inducible Early Gene (TIEG): A Candidate Tumor Suppressor or Cell Cycle Regulator? Thomas e. Spelsberg, Malayannan Subramaniam, Katrina M. Waters, Theresa E. Hefferan, David J. Rickard, and Gregory G. Reinholz ......................... .
231
238
250
xvi Contents
PART 7. AROMATASE: IMPLICATIONS FOR BREAST CANCER. . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . 261
Introduction Aromatase: Implications for Breast Cancer Gregory A. Reed . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263
20
21
22
Control of Estrogen Biosynthesis in Breast Cancer Shiuan Chen, Dujin Zhou, Yeh-Chih Kao, Chun Yang, and Baiba Grube ................................... .
Regulation of Aromatase in Normal and Malignant Breast Tissues: The Role of the Immune System A. Singh, A. Purohit, M.W. Ghilchik, and MJ. Reed .....
Regulation of Aromatase in Breast Cancer and Correlation of Aromatase and Cyc100xygenase Gene Expression Robert W. Brueggemeier, Anne L. Quinn, Yasuro Sugimoto, Young C. Lin, Michelle L. Parrett, Farahnaz S. Joarder, Randell E. Harris, and Fredika M. Robertson ............................ .
PART 8. ORGAN SITE:
267
277
285
PROSTATE/OVARy.............................. 299
Introduction Androgen Receptor and its Role in the Development and Control of Androgen-independent Prostate Cancer Shutsung Liao, John M. Kokontis, and Richard A. Hiipakka 301
23 Etiologic Mechanisms in Epithelial Ovarian Cancer Harvey A. Risch ••••••••••••••••••••••••••••••••• 307
24
25
Stromal Influences in Prostatic Carcinogenesis Gerald R. Cunha, Simon W. Hayward, Thea Tisty, and Gary D. Grossfeid ............................... .
Androgen Receptor Structure and Function in Prostate Cancer Grant Buchanan and Wayne D. Tilley ................ .
320
333
Contents xvii
PART 9. OSTEOPOROSIS AND ESTROGENS ...................................... 343
Introduction Hormone Replacement Therapy: A Clinical Overview James H. Pickar. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 345
26
27
Role of Estrogen and Bone Morphogentic Protein Signaling in Osteoblast Differentiation Stephen E. Harris ............................... .
Estrogens and the Skeleton Michael Kleerekoper ............................. .
PART 10. CARDIOVASCULAR DISEASE AND
348
357
ESTROGENSIPROGESTINS . . . . . . . . . . . . . . . . . . . . . . 363
28
29
Mechanisms of Estrogen Action on the Cardiovascular System John C. Stevenson ............................... .
Atherosclerosis and Hormone Replacement Therapy: The Role of Estrogen in Secondary Prevention of Cardiovascular Events Jay M. Sullivan ................................. .
365
372
VIEWPOINT ...................................... 383
30 Long-term Hormone Replacement Therapy: A Contrary Point of View Jacques E. Rossouw .............................. 385
EPILOGUE ........................................ 401
31 A Unified General Mechanism for Hormonal Carcinogenesis Begins to Emerge Jonathan 1. Li and Sara Antonia Li ................... 403
xviii Contents
COMMUNICATIONS
Session I. EpidemiologylHuman Studies . . . . . . . . . . . . . . 407
The Risk of Postmenopausal Breast Cancer After Estrogen and Estrogen-Progestin Replacement C. Magnusson, Ingemar R. Persson, E. Weiderpass, and N. Correia. 409
No Significant Difference in Age at Menarche, Menstrual Cycle Length, Age at First Full Term Pregnancy, and Nulliparity among BRCAI Mutation Carriers Compared with Their Unaffected Relatives Helena Jernstrom, O. Johannsson, Ake Borg, and H. Olsson ...... 413
Cell Proliferation and Apoptosis in the Normal Breast Epithelium of Pre, Peri, and Postmenopausal Women Seema A. Khan and Scott Stickles .......................... 418
Expression and Estrogen Inducible Promoter Activity of Human Estrogen-responsive Finger Protein Gene in Breast and Ovarian Cancer Cells Kazuhiro Ikeda, Satoshi Inoue, Akira Orimo, Hiroi Fujiko Tsuchiya, Itsuo Gorai, Yasuhiro Higashi, and Masarni Muramatsu ......... 424
Novel SmaIl Molecule IL-6 Inhibitors as Anti-Cancer Drugs Bernd Stein, May Sutherland, Stephanie Lipps, Joseph Lewcock, Helen Brady, and Lynn Ransone..... . . . ..... .... . . . . . . . . . . . 429
Session II. Metabolism Studies/Cellular & Molecular Biology ................................... 435
Cellular Transforming Activity and Genotoxic Effects of 17p-Estradiol and Its Eight Metabolites in Syrian Hamster Embryo Cells Takeki Tsutsui, Yukiko Tamura, and J. Carl Barrett ............ 437
Evidence for an Initiation Mechanism of 17P Estradiol Carcinogenesis Fu-Li Yu, Mian-Ying Wang, and Wanda Bender ............... 444
Estradiol Metabolism by Rat Liver Microsomes from Strains Differing in Susceptibility to Mammary Carcinogenesis
Contents xix
Gregory A. Reed, Angela M. Wilson, and Janete K. Padgitt. . . . . . . 451
Induction of Breast Cancer in Noble Rats with a Combination of Estrogen and Testosterone Y.C. Wong, B. Xie, and S.W. Tsao ......................... 456
Isolation and Purification of Breast Carcinoma Cell Lines from a Noble Rat B. Xie, S.W. Tsao, and Y.c. Wong ......................... 464
The ACI Rat as a Genetically Defined Animal Model for the Study of Estrogen Induced Mammary Cancers Martin Tochacek, Eric A. VanderWoude, Thomas J. Spady, Djuana M.E. Harvell, Mary C. Snyder, Karen L. Pennington, Tanya M. Reindl, and James D. Shull. . . . . . . . . . . . . . . . . . . . . . . . 471
Characteristics of Dehydroepiandrosterone-induced Hepatocarcinogenesis in the Rat Doris Mayer, Christel Metzger, Dirk Nehrbass, and Peter Bannasch 477
Hepatic Toxicity of Estrogen in Armenian and Chinese Hamsters John E. Coe, Kamal G. Ishak, and MJ. Ross... . . ... . . . . . . . . . . 484
Suppression of Liver Tumor Formation by the Liver Microenvironment of Female, but Not Male, Syngeneic Hosts Gary J. Smith, Sharon C. Presnell, William B. Coleman, and Joe W. Grisham ..................................... 489
Dietary Energy Restriction Inhibits Estrogen Induced Pituitary Tumorigenesis in a Rat Strain Specific Manner Djuana M.E. Harvell, Thomas J. Spady, Tracy E. Strecker, Athena M. Lemus-Wilson, Karen L. Pennington, Fangchen Shen, Diane F. Birt, Rodney D. McComb, and James D. Shull ......... 496
Estrogen-induced Prolactinoma Development: A Role for Cell-Cell Communication Shane T. Hentges and Dipak K. Sarkar . . . . . . . . . . . . . . . . . . . . . . . 502
xx Contents
Combined Administration of Transplacental Ethylnitrosourea and Postnatal Diethylstilbestrol Induce Neural Differentiation in Interstitial Celis of the Golden Hamster Kidney Amando Peydro-Olaya, Carmen Carda, and Antonio Llombart-Bosch ................................. 509
Aromatase Overexpression: Is Aromatase an Oncogene? Rajeshwar Rao Tekmal, Kiran Gill, and Nameer Kirma . . . . . . .... 514
Genetic Toxicity In Vitro of Bisphenol A-Diglycidyletber (BADGE) and its Hydrolysis Products Erika Pfeiffer and Manfred Metzler ......................... 521
Lack of Genotoxicity of Major Mammalian and Plant Lignans at Various Endpoints In Vitro Sabine E. Kulling, Eric Jacobs, and Manfred Metzler ........... 527
Index 533
Participants
C. MARCELO ALDAZ Department of Carcinogenesis, MD Anderson, Science Park, University of Texas, Smithville, TX, USA
BENJAMIN D. ANDERSON University of Washington, Seattle, WA, USA
GARNET ANDERSON Fred Hutchinson Cancer Research Center, Seattle, W A, USA
1. CARL BARRETT Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA
HELEN BRADY Bone Metabolism and Functional Genomics, Signal Pharmaceuticals, San Diego, CA, USA
ROBERT W. BRUEGGEMEffiR College of Pharmacy, The Ohio State University, Columbus, OH, USA
TRUDY BUSH Department of Epidemiology, University of Maryland, Baltimore, MD,USA
CHU CHEN Fred Hutchinson Cancer Research Center, Seattle, W A, USA
SHIUAN CHEN Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA
BARBARA COCHRANE Fred Hutchinson Cancer Research Center, Seattle, W A, USA
JOHNE. COE Laboratory of Persistent Viral Diseases, NIAID, Hamilton, MT, USA
GRAHAM A. COLDITZ Channing Laboratory, Brigham and Women's Hospital, Boston, MA, USA
xxi
xxii Participants
SlEVEN 1. COlLINS Fred Hutchinson Cancer Research Center, Seattle, W A, USA
EVA COREY Department of Urology , University of Washington, Seattle, W A, USA
GERALD R. CUNHA Department of Anatomy, University of California, San Francisco, CA, USA
JANET R. DAUNG Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, W A, USA
RICHARD P. DIAUGUSTINE Laboratory of Biochemical Risk Assessment, National Institute ofEnvironmental Health Sciences, NIH, Research Triangle Park, NC, USA
YVONNE DRAGAN School of Public Health, Ohio State University, Columbus, OH, USA
JACK FISHMAN Department of Biochemistry, Rockefeller University, New York, NY, USA
ANNETlE FITzPATRICK Department of Biostatistics, University of Washington, Seattle, W A, USA
PATRICK FRIEL Department of Genetics and Cell Biology, Washington State University, Pullman, W A, USA
ROBIN FuCHS-YOUNG University of Texas, MD Anderson Cancer Center, Smithville, TX, USA
HIROMI FUJITA Nakano Eye Clinic, Kyoto, Japan
JACK GORSKI Department of Biochemistry, University of Wisconsin, Madison, WI, USA
BAlBI GRUBE Division of Immunology, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA
JAN-AKE GUSTAFSSON Department of Medical Nutrition, Huddinge University Hospital, NOVUM, Huddinge, Sweden
SlEPHEN E. HARRIS Division of Endocrinology, University of Texas, San Antonio, TX,USA
Participants xxiii
LEE HARTWELL Fred Hutchinson Cancer Research Center, Seattle, W A, USA
NEILANN HENDERSON Fred Hutchinson Cancer Research Center, Seattle, W A, USA
ROBERT N. HOOVER Environmental Epidemiology Branch, National Cancer Institute, NIH, Bethesda, MD, USA
CHAD E. HUDSON Department of Microbiology, Medical University of South Carolina, Charleston, SC, USA
FRIEDRICH HUSMANN Division of Endocrinology, Klinik am Malerwinkel, Bad Sassendorf, Germany
KAzUIDRO IKEDA Department ofBiochemistry, Saitama Medical School, Saitama, Japan
HERBERT JACOBSON Reproductive Studies Laboratory, Albany Medical College, Albany, NY, USA
ELWOOD V. JENSEN IHF Institute for Hormone and Fertility Research, Hamburg, Germany
HELENAJERNSTROM Department of Oncology, University of Lund, Lund, Sweden
Ow-Po KAwONIEMI Laboratory of Cancer Genetics, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
MARION KAVANAUGH-LYNCH University of California, Oakland, CA, USA
SEEMA A. KHAN Department of Surgery, Northwestern Memorial Hospital, Chicago, IL, USA
MICHAEL KLEEREKOPER Division of Endocrinology, Wayne State University, Detroit, MI, USA
ALAN R. KRISTAL Fred Hutchinson Cancer Research Center, Seattle, WA, USA
SABINE E. KUWNG Institute of Food Chemistry, University of Karlsruhe, Karlsruhe, Germany
SUE-MIN LAI Department of Preventative Medicine, Kansas Cancer Institute, University of Kansas Medical Center, Kansas City, KS, USA
JOHANNA LAMPE Fred Hutchinson Cancer Research Center, Seattle, W A, USA
xxiv Participants
JONATHAN J. LI Division of Etiology and Prevention of Hormonal Cancers, University of Kansas Medical Center, Kansas City, KS, USA
SARA ANTONIA LI Division of Etiology and Prevention of Hormonal Cancers, University of Kansas Medical Center, Kansas City, KS, USA
SHUTSUNG LIAO The Ben May Institute for Cancer Research, University of Chicago, Chicago, IL, USA
ANTONIO LLOMBART-BosCH Department of Pathology, Instituto Valenciano de Oncologia, University of Valencia, Valencia, Spain
MARGARET MADELEINE Fred Hutchinson Cancer Research Center, Seattle, W A, USA
KATHY E. MALONE Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, W A, USA
MARGARETT. MANDELSON Center for Health Studies, University of Washington, Seattle, W A, USA
POLLY A. MARCHBANKS Centers for Disease Control, Atlanta, GA, USA
CHARLES P. MARTUCCI Strang Cancer Research Laboratory, Rockefeller University, New York, NY, USA
DORIS MAYER Division of Cell Pathology, Deutsches Krebsforschungszentrum, Heidelberg, Germany
ANNE McTIERNAN Fred Hutchinson Cancer Research Center, Seattle, W A, USA
MANFRED ME1ZLER Laboratory of Environmental Toxicology, Department of Chemistry, University of Kaiserslautern, Germany
ANDREI MIKHEEV Fred Hutchinson Cancer Research Center, Seattle, W A, USA
SURESHMoHLA National Institutes of Health, National Cancer Institute, Rockville, MD, USA
GERALD C. MUELLER McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI, USA
SATYABRATA NANDI Cancer Research Laboratory, University of California, Berkeley, CA, USA
Participants xxv
POlLY A. NEWCOMB Fred Hutchinson Cancer Research Center, Seattle, W A, USA
JAMES S. NORRIS Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA
ELAINE OSTRANDER Fred Hutchinson Cancer Research Center, Seattle, W A, USA
ARTHUR B. PARDEE Dana-Farber Cancer Institute, Harvard University, Boston, MA,USA
INGEMAR R. PERSSON Department of Medical Epidemiology, Stockholm, Sweden
ERIKA PFEIFFER Institute of Food Chemistry, University of Karlsruhe, Kalrsruhe, Germany
JAMES H. PICKAR Clinical Research and Development, Wyeth-Ayerst Research, Philadelphia, PA, USA
HENRY C. PITOT McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI, USA
PEGGY PORTER Fred Hutchinson Cancer Research Center, Seattle, W A, USA
OWEN W.J. PRAlL Cancer Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, Australia
GREGORY A. REED Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA
M. J. REED Unit of Metabolic Medicine, Imperial College, London, United Kingdom
JUERGEN K.V. REICHARDT Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA, USA
HARVEY A. RISCH Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT, USA
HENRI ROCHEFORT INSERM U 148, Montpellier, France
MARIANNA RODOVA Division of Etiology and Prevention of Hormonal Cancers, University of Kansas Medical Center, Kansas City, KS, USA
xxvi Participants
JEFFREY M. ROSEN Department of Cell Biology, Baylor College of Medicine, Houston, TX, USA
MARY ANNE ROSSING Fred Hutchinson Cancer Research Center, Seattle, W A, USA
JACQUES E. Rossouw Office of Prevention, Bethesda, MD, USA
CAROLYN RUTIER Center for Health Studies, Seattle, W A, USA
DIPAK K. SARKAR Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA, USA
DAVID A. SCHWARlZ Department of Microbiology, Medical University of South Carolina, Charleston, SC, USA
STEPHEN SCHW ARIZ Fred Hutchinson Cancer Research Center, Seattle, W A, USA
LEA I. SEKELY National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
ROBERT P. C. SHm Protein and Polypeptide Hormone Laboratory, University of Manitoba, Winnipeg, Canada
JAMES D. SHUlL Cancer Institute, University of Nebraska Medical Center, Omaha, NE,USA
PENTTI SIITERI Somona, CA, USA
GARY J. SMITH Department of Pathology, University of North Carolina, Chapel Hill, NC, USA
THOMAS C. SPELSBERG Department of Biochemistry and Molecular Biology, Mayo Graduate School of Medicine, Rochester, MN, USA
GEORGE M. STANCEL Department of Integrative Biology, Pharmacology, and Physiology, University of Texas Medical School, Houston, TX, USA
JANETL. STANFORD Division of Public Helath Sciences, Fred Hutchinson Cancer Research Center, Seattle, W A, USA
BERND STEIN Bone Metabolism and Functional Genomics, Signal Pharmaceuticals, Inc., San Diego, CA, USA
Participants xxvii
JOHN C. STEVENSON Cecil Rosen Research Laboratories, Imperial College School of Medicine, London, United Kingdom
JAY M. SUWVAN Cardiovascular Diseases, University of Tennessee, Memphis, TN,USA
KALY AN SUNDARAM Central Biomedical Research, Population Council, New York, NY,USA
ROBERT L. SUTHERLAND Cancer Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, Australia
RAJESHWAR RAO TEKMAL Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA
DAVID B. THOMAS Fred Hutchinson Cancer Research Center, Seattle, W A, USA
WAYNE D. TILLEy Flinders Cancer Centre, Division of Surgery, Flinders Medical Centre, Bedford Park, Australia
MARTIN TOCHACEK Cancer Institute, University of Nebraska Medical Center, Omaha, NE, USA
TAKEKI TSUTSUI The Nippon Dental University, Department of Pharmacology, Tokyo, Japan
PRISCIlLA VELENTGAS Cardiovascular Health Study, University of Washington, Seattle, W A, USA
FREDERIC M. WALDMAN Department of Laboratory Medicine, University of California - San Francisco, San Francisco, CA, USA
CHERYL LYN WALKER Department of Carcinogenesis. MD Anderson Cancer Center, Smithville, TX, USA
MIAN-YING WANG Department of Biomedical Sciences, mc College of Medicine, Rockford, IL, USA
NOEL S. WEISS Fred Hutchinson Cancer Research Center. Seattle, W A, USA
ALESSANDRO WEISZ Instituto di Patologia Generale e Oncologia, Seconda Universita degli Studi di Napoli, Napoli. Italy
xxviii Participants
HEATHER-MARIE P. WILSON Department of Pathology, University of Washington, Seattle, W A, USA
Y.C. WONG Department of Anatomy, University of Hong Kong, Hong Kong, Peoples Republic of China
B. XIE Department of Anatomy, University of Hong Kong, Hong Kong, Peoples Republic of China
CHUN YANG Division of Immunology, Beckman Research Institute; City of Hope National Medical Center, Duarte, CA, USA
YUTAKA YASUI Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Fu-LI Yu Department of Biomedical Sciences, UIC College of Medicine, Rockford, IL, USA
DUJIN ZHOU Division of Immunology, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA
Contributors
RAFFAELEADDEO Instituto di Patologia Generale e Oncologia. Seconda Universita degli Studi di Napoli. Napoli. Italy
C. MARCELO ALoAZ Department of Carcinogenesis. MD Anderson. Science Park. University of Texas. Smithville. TX. USA
LUCIA ALruCCI Instituto di Patologia Generale e Oncologia. Seconda Universita degli Studi di Napoli. Napoli. Italy
MAsSIMoANCORA Instituto di Patologia Generale e Oncologia. Seconda Universita degli Studi di Napoli. Napoli. Italy
BENJAMIN D. ANDERSON University of Washington. Seattle. WA. USA
GARNET ANDERSON Fred Hutchinson Cancer Research Center. Seattle. W A. USA
PETERBANNASCH Division of Cell Pathology. Deutsches Krebsforschungszentrum, Heidelberg. Germany
J. CARL BARRETI Laboratory of Molecular Carcinogenesis. NIEHS. Research Triangle Park. NC. USA
ANDRZEJ BEDNAREK Department of Carcinogenesis. MD Anderson. Science Park. University of Texas. Smithville. TX. USA
WANDA BENDER Department of Biomedical Sciences. mc College of Medicine. Rockford. IL. USA
DIANEF. BIRT Center for Designing Foods. Ames. IA. USA
DEBAJIT K. BISWAS Dana-Farber Cancer Institute. Harvard Medical School. Boston. MA. USA
xxix
xxx Contributors
HOll.YL. BOETIGER-TONG Department ofIntegrative Biology, Pharmacology, and Physiology, University of Texas Medical School, Houston, TX, USA
AKE BORG Department of Oncology, University of Lund, Lund, Sweden
RAPHAElLE BORGO Instituto di Patologia Generale e Oncologia, Seconda Universita degli Studi di Napoli, Napoli, Italy
HELEN BRADY Bone Metabolism and Functional Genomics, Signal Pharmaceuticals, Inc., San Diego, CA, USA
FRANCESCO BRESCIANI Instituto di Patologia Generale e Oncologia, Seconda Universita degli Studi di Napoli, Napoli, Italy
ROBERT W. BRUEGGEMEffiR College of Pharmacy, Ohio State University, Columbus, OH, USA
LUKAS BUBENDORF Laboratory of Cancer Genetics, National Human Genome Research Institute, National Institute of Health, Bethesda, MD, USA
GRANT BUCHANAN Flinders Cancer Centre, Division of Surgery, Flinders Medical Centre, Bedford Park, Australia
TRUDY BUSH Department of Epidemiology, University of Maryland, Baltimore, MD,USA
MASSIMO CANCEMI Instituto di Patologia Generale e Oncologia, Seconda Universita degli Studi di Napoli, Napoli, Italy
MARILYN CANSLER Department of Pathology, University of Kansas Medical Center, Kansas City, KS, USA
CARMEN CARDA Department of Pathology, Instituto Valenciano de Oncologia, University of Valencia, Valencia, Spain
APRIL CHARPENTmR Department of Carcinogenesis, MD Anderson, Science Park, University of Texas, Smithville, TX, USA
CHU CHEN Fred Hutchinson Cancer Research Center, Seattle, W A, USA
SHIUAN CHEN Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA
Contributors xxxi
T AE-YON CHUN Department of Biochemistry, University of Wisconsin, Madison, WI, USA
LUIGI CICA TIElLO Instituto di Patologia Generale e Oncologia, Seconda Universita degli Studi di Napoli, Napoli, Italy
BARBARA COCHRANE Fred Hutchinson Cancer Research Center, Seattle, W A, USA
JOHNE. COE Laboratory of Persistent Viral Diseases, NIAID, Hamilton, MT, USA
GRAHAM A. COLDrrz Channing Laboratory, Brigham and Women's Hospital, Boston, MA, USA
WILLIAM B. COLEMAN Department of Pathology, University of North Carolina, Chapel Hill, NC, USA
STEVEN J. COWNS Fred Hutchinson Cancer Research Center, Seattle, W A, USA
EVA COREY Department of Urology , University of Washington, Seattle, W A, USA
N. CORREIA Department of Medical Epidemiology, Stockholm, Sweden
GERALD R. CUNHA Department of Anatomy, University of California, San Francisco, CA, USA
KARA CUSHING Fred Hutchinson Cancer Research Center, Seattle, W A, USA
JANET R. DALING Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
RICHARD P. DIAuGUSTINE Laboratory of Biochemical Risk Assessment, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA
YVONNE P. DRAGAN School of Public Health, Ohio State University, Columbus, OH, USA
D. DUDIK Protein and Polypeptide Hormone Laboratory, University of Manitoba, Winnipeg, Canada
JACK FISHMAN Department of Biochemistry, Rockefeller University, New York, NY, USA
ANNETrE FITZPATRICK Department of Biostatistics, University of Washington, Seattle, W A, USA
xxxii Contributors
HEIDE L. FORD Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
PATRICK FRIEL Department of Genetics and Cell Biology, Washington State University, Pullman, WA, USA
ROBIN FUCHS-YOUNG University of Texas, MD Anderson Cancer Center, Smithville, TX, USA
HIROMI FuJITA Nakano Eye Clinic, Kyoto, Japan
M.W. GHILCHIK Unit of Metabolic Medicine, Imperial College, London, United Kingdom
KIRAN GILL Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA
ITSUO GORAl Department of Biochemistry, Saitama Medical School, Saitama, Japan
JACK GORSKI Department of Biochemistry, University of Wisconsin, Madison, WI, USA
JOEW. GRISHAM Department of Pathology, University of North Carolina, Chapel Hill, NC, USA
GARY D. GROSSFELD Department of Anatomy, University of California, San Francisco, CA, USA
BAIBA GRUBE Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA
JAN-A.KE GUSTAFSSON Department of Medical Nutrition, Huddinge University Hospital, NOVUM, Huddinge, Sweden
RAPHAEL GUZMAN Department of Molecular and Cell Biology, University of California, Cancer Research Lab, Berkeley, CA, USA
RANDALLE. HARRIS College of Pharmacy, Ohio State University, Columbus, OH, USA
STEPHEN E. HARRIS Division of Endocrinology, University of Texas, San Antonio, TX,USA
Contributors xxxiii
LEE HARTWELL Fred Hutchinson Cancer Research Center, Seattle, WA, USA
DJUANAM.E. HARVELL Cancer Institute, University of Nebraska Medical Center, Omaha, NE, USA
KATHLEEN HA WKlNS Department of Carcinogenesis, MD Anderson, Science Park, University of Texas, Smithville, TX, USA
SIMON W. HAYWARD Department of Anatomy, University of California, San Francisco, CA, USA
THERESAE.HEFFERAN Department of Biochemistry and Molecular Biology, Mayo Graduate School of Medicine, Rochester, MN, USA
NEILANN HENDERSON Fred Hutchinson Cancer Research Center, Seattle, W A, USA
SHANE T. HENTGES Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA, USA
YASUHIRO HIGASHI Department of Biochemistry, Saitama Medical School, Saitama, Japan
RICHARD A. HIIPAKKA The Ben May Institute, Chicago, IL, USA
HISAHIKO HIROI Department of Biochemistry, Saitama Medical School, Saitama, Japan
ROBERT N. HOOVER Environmental Epidemiology Branch, National Cancer Institute, NIH, Bethesda, MD, USA
CHAD E. HUDSON Department of Microbiology, Medical University of South Carolina, Charleston, SC, USA
FRIEDRICH HUSMANN Division of Endocrinology, Klinik am Malerwinkel, Bad Sassendorf, Germany
SALMAN M. HYDER Department of Integrative Biology, Pharmacology, and Physiology, University of Texas Medical School, Houston, TX, USA
KAzUHIRO IKEDA Department of Biochemistry, Saitama Medical School, Saitama, Japan
SATOSHI INOUE Department of Biochemistry, Saitama Medical School, Saitama, Japan
xxxiv Contributors
KAMAL G. ISHAK Laboratory of Persistent Viral Diseases, NIAlD, Hamilton, MT, USA
B. IWASIOW Protein and Polypeptide Hormone Laboratory, University of Manitoba, Winnipeg, Canada
ERIC JACOBS Institute of Food Chemistry, University of Karlsruhe, Karlsruhe, Germany
HERBERT JACOBSON Reproductive Studies Laboratory, Albany Medical College, Albany, NY, USA
ELWOOD V. JENSEN IHF Institute for Hormone and Fertility Research, Hamburg, Germany
HELENAJERNSTROM Department of Oncology, University of Lund, Lund, Sweden
FARAHNAZ S. JOARDER College of Pharmacy, Ohio State University, Columbus, OH, USA
O. JOHANNSSON Department of Oncology, University of Lund, Lund, Sweden
THORA JONNASDOTTIR Fred Hutchinson Cancer Research Center, Seattle, WA, USA
V. CRAIG JORDAN Robert H. Lurie Cancer Center, Northwestern University Medical School, Chicago, IL, USA
OLLI-P KALLIONIEMI Laboratory of Cancer Genetics, National Human Genome Research Institute, National Institute of Health, Bethesda, MD, USA
YEH-CHIH KAo Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA
MARION KAVANAUGH-LYNCH University of California, Oakland, CA, USA
SEEMA A. KHAN Department of Surgery, Northwestern Memorial Hospital, Chicago, IL, USA
NAMEER KIRMA Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA
MICHAEL KLEEREKOPER Division of Endocrinology, Wayne State University, Detroit, MI, USA
Contributors xxxv
DIANE M. KLoTZ Laboratory of Biochemical Risk Assessment, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA
JOHN M. KOKONTIS The Ben May Institute, Chicago, IL, USA
ALAN R. KRISTAL Fred Hutchinson Cancer Research Center, Seattle, WA, USA
SABINE E. KUll..ING Institute of Food Chemistry, University of Karlsruhe, Karlsruhe, Germany
KENDRA LAFLIN Department of Carcinogenesis, MD Anderson, Science Park, University of Texas, Smithville, TX, USA
SUE-MIN LAI Department of Preventative Medicine, Kansas Cancer Institute, University of Kansas Medical Center, Kansas City, KS, USA
JOHANNA LAMPE Fred Hutchinson Cancer Research Center, Seattle, W A, USA
ATHENA M. LEMUS-WILSON Cancer Institute, University of Nebraska Medical Center, NE, USA
JOSEPH LEWCOCK Bone Metabolism and Functional Genomics, Signal Pharmaceuticals, Inc., San Diego, CA, USA
JUAN LEYVA Instituto di Patologia Generale e Oncologia, Seconda Universita degli Studi di Napoli, Napoli, Italy
DONG-HUI LI McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI, USA
JONATHAN J. LI Division of Etiology and Prevention of Hormonal Cancers, University of Kansas Medical Center, Kansas City, KS, USA
SARA ANTONIA LI Division of Etiology and Prevention of Hormonal Cancers, University of Kansas Medical Center, Kansas City, KS, USA
DEZHONGJOSHUALIAO Lombardi Cancer Center, Georgetown University Medical Center, Washington, D.C., USA
SHUTSUNG LIAO The Ben May Institute for Cancer Research, University of Chicago, Chicago, IL, USA
YOUNG C. LIN College of Pharmacology, Ohio State University, Columbus, OH, USA
xxxvi Contributors
STEPHANffi LIPPS Bone Metabolism and Functional Genomics, Signal Pharmaceuticals, Inc., San Diego, CA, USA
ANTONIO LLOMBART-BoSCH Department of Pathology, Instituto Valenciano de Oncologia, University of Valencia, Valencia, Spain
MICHAEL MACLEOD Department of Carcinogenesis, MD Anderson, Science Park, University of Texas, Smithville, TX, USA
MARGARET MADELEINE Fred Hutchinson Cancer Research Center, Seattle, W A, USA
C. MAGNUSSON Department of Medical Epidemiology, Stockholm, Sweden
SARI MAKELA Department of Integrative Biology, Pharmacology, and Physiology, University of Texas Medical School, Houston, TX, USA
KATHLEEN E. MALONE Fred Hutchinson Cancer Research Center, Seattle, WA, USA
MARGARETT. MANDELSON Center for Health Studies, University of Washington, Seattle, W A, USA
POIl..Y A. MARCHBANKS Centers for Disease Control, Atlanta, GA, USA
KATHERINE J. MARTIN Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
CHARLES P. MARTUCCI Strang Cancer Research Laboratory, Rockefeller University, New York, NY, USA
DORIS MAYER Division of Cell Pathology, Deutsches Krebsforschungszentrum, Heidelberg, Germany
RODNEY D. MCCOMB Cancer Institute, University of Nebraska Medical Center, NE,USA
ANNE McTIERNAN Fred Hutchinson Cancer Research Center, Seattle, W A, USA
CHRISTEL METZGER Division of Cell Pathology, Deutsches Krebsforschungszentrum, Heidelberg, Germany
MANFRED METzI..ER Institute of Food Chemistry, University of Karlsruhe, Karlsruhe, Germany
Contributors xxxvii
ANDREI MIKHEEV Fred Hutchinson Cancer Research Center, Seattle, W A, USA
SURESHMOHLA National Institutes of Health, National Cancer Institute, Rockville, MD, USA
GERALD C. MUElLER McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI, USA
MASAMI MURAMATSU Department of Biochemistry, Saitama Medical School, Saitama, Japan
KRISTEN L. MURPHEY Department of Cell Biology, Baylor College of Medicine, Houston, TX, USA
EUZABETH A. MUSGROVE Cancer Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, Australia
SATYABRATA NANDI Cancer Research Laboratory, University of California, Berkeley, CA, USA
DIRKNEHRBASS Division of Cell Pathology, Deutsches Krebsforschungszentrum, Heidelberg, Germany
POlLY A. NEWCOMB Fred Hutchinson Cancer Research Center, Seattle, W A, USA
JAMES S. NORRIS Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA
EMILE NUWAYSIR McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI, USA
H. OLSSON Department of Oncology, University of Lund, Lund, Sweden
AKIRA ORIMO Department of Biochemistry, Saitama Medical School, Saitama, Japan
ELAINE OSTRANDER Fred Hutchinson Cancer Research Center, Seattle, W A, USA
JANETTE K. PADGm Department of Pharmacology , Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA
ARTHUR B. PARDEE Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
MICHElLE L. PARRETT College of Pharmacy, Ohio State University, Columbus, OH,USA
xxxviii Contributors
KAREN L. PENNINGTON Cancer Institute, University of Nebraska Medical Center, Omaha, NE, USA
INGEMAR R. PERSSON Department of Medical Epidemiology, Stockholm, Sweden
VALERIA BELSITO PETRIZZI Instituto di Patologia Generale e Oncologia, Seconda Universita degli Studi di Napoli, Napoli, Italy
AMANDO PEYDRO-OLAYA Department of Pathology, Instituto Valenciano de Oncologia, University of Valencia, Valencia, Spain
ERIKA PFEIFFER Institute of Food Chemistry, University of Karlsruhe, Karlsruhe, Germany
JAMES H. PICKAR Clinical Research and Development, Wyeth-Ayerst Research, Philadelphia, PA, USA
HENRY C. PITOT McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI, USA
PEGGY L. PORTER Fred Hutchinson Cancer Research Center, Seattle, W A, USA
OWEN W.J. PRAlL Cancer Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, Australia
SHARON C. PRESNElL Department of Pathology, University of North Carolina, Chapel Hill, NC, USA
A. PUROHIT Unit of Metabolic Medicine, Imperial College, London, United Kingdom
ANNEL. QUINN College of Pharmacy, Ohio State University, Columbus, OH, USA
LAKSHMANASWAMY RAJKUMAR Cancer Research Laboratory, University of California, Berkeley, CA, USA
LYNN RANSONE Bone Metabolism and Functional Genomics, Signal Pharmaceuticals, Inc., San Diego, CA, USA
GREGORY A. REED Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA
M.J. REED Unit of Metabolic Medicine, Imperial College, London, United Kingdom
Contributors xxxix
JUERGEN K.V. REICHARDT Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA, USA
TANYA M. REINDL Cancer Institute, University of Nebraska Medical Center, Omaha, NE, USA
GREGORY G. REINHOLZ Department of Biochemistry and Molecular Biology, Mayo Graduate School of Medicine, Rochester, MN, USA
R. GREGG RICHARDS Laboratory of Biochemical Risk Assessment, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA
DAVID 1. RICKARD Department of Biochemistry and Molecular Biology, Mayo Graduate School of Medicine, Rochester, MN, USA
HARVEY A. RISCH Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT, USA
FREDIKA M. ROBERTSON College of Pharmacology, The Ohio State University, Columbus, OH, USA
HENRI ROCHEFORT INSERM U 148, Montpellier, France
MARIANNA RODOVA Division of Etiology and Prevention of Hormonal Cancers, University of Kansas Medical Center, Kansas City, KS, USA
EILEEN M. ROGAN Cancer Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, Australia
JEFFREY M. ROSEN Department of Cell Biology, Baylor College of Medicine, Houston, TX, USA
M.J. Ross Laboratory of Persistent Viral Diseases, NIAID, Hamilton, MT, USA
MARY ANNE ROSSING Fred Hutchinson Cancer Research Center, Seattle, W A, USA
JACQUES E. Rossouw Office of Prevention, Bethesda, MD, USA
CAROLYN RUTTER Center for Health Studies, Seattle, W A, USA
RUTH SAGER Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
LINDA SARGENT McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI, USA
xl Contributors
DIPAK K. SARKAR Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA, USA
DAVID A. SCHWARTZ Department of Microbiology, Medical University of South Carolina, Charleston, SC, USA
STEPHEN SCHWARTZ Fred Hutchinson Cancer Research Center, Seattle, W A, USA
LEA I. SEKELY National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
FANGCHEN SHEN Cancer Institute, University of Nebraska Medical Center, NE, USA
ROBERT P.C. SHIV Protein and Polypeptide Hormone Laboratory, University of Manitoba, Winnipeg, Canada
JAMES D. SHULL Cancer Institute, University of Nebraska Medical Center, Omaha, NE, USA
PENTTI SUTERI Somona, CA, USA
A. SINGH Unit of Metabolic Medicine, Imperial College, London, United Kingdom
GARY J. SMITH Department of Pathology, University of North Carolina, Chapel Hill, NC, USA
MARY C. SNYDER Cancer Institute, University of Nebraska Medical Center, Omaha, NE, USA
THOMAS J. SPADY Cancer Institute, University of Nebraska Medical Center, Omaha, NE, USA
J. SPARLING Protein and Polypeptide Hormone Laboratory, University of Manitoba, Winnipeg, Canada
THOMAS C. SPELSBERG Department ofB iochemistry and Molecular Biology, Mayo Graduate School of Medicine, Rochester, MN, USA
GEORGE M. STANCEL Department of Integrative Biology, Pharmacology, and Physiology, University of Texas Medical School, Houston, TX, USA
JANETL. STANFORD Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, W A, USA
Contributors xli
BERND STEIN Bone Metabolism and Functional Genomics, Signal Pharmaceuticals, Inc., San Diego, CA, USA
JOHN C. STEVENSON Cecil Rosen Research Laboratories, Imperial College School of Medicine, London, United Kingdom
SCOTT STICKLES University Surgical Associates, SUNY Health Science Center, Syracuse, NY, USA
TRACyE. STRECKER Cancer Institute, University of Nebraska Medical Center, NE, USA
MALAYANNAN SUBRAMANIAM Department of Biochemistry and Molecular Biology, Mayo Graduate School of Medicine, Rochester, MN, USA
YASURO SUGIMOTO College of Pharmacology, The Ohio State University, Columbus, OH, USA
JAY M. SUWV AN Cardiovascular Diseases, University of Tennessee, Memphis, TN,USA
KAL Y AN SUNDARAM Central Biomedical Research, Population Council, New York, NY,USA
NICOLA M. SUTER Fred Hutchinson Cancer Research Center, Seattle, W A, USA
MAY SUTHERLAND Bone Metabolism and Functional Genomics, Signal Pharmaceuticals, Inc., San Diego, CA, USA
ROBERT L. SUTHERLAND Cancer Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, Australia
YUKIKO TAMURA The Nippon Dental School, Department of Pharmacology, Tokyo, Japan
RAJESHW AR RAo TEKMAL Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA
DAVID B. THOMAS Fred Hutchinson Cancer Research Center, Seattle, WA, USA
GUDMUNDUR THORDARSON Cancer Research Laboratory, University of California, Berkeley, CA, USA
xlii Contributors
WAYNE D. TJU..EY Flinders Cancer Centre, Division of Surgery, Flinders Medical Centre, Bedford Park, Australia
THEA TLSTY Department of Anatomy, University of California, San Francisco, CA,USA
MARTIN TOCHACEK Cancer Institute, University of Nebraska Medical Center, Omaha, NE, USA
S.W. TSAO Department of Anatomy, University of Hong Kong, Hong Kong, Peoples Republic of China
FUJIKO TSUCHIYA Department of Biochemistry , Saitama Medical School, Saitama, Japan
TAKEKITSUTSUI The Nippon Dental School, Department of Pharmacology, Tokyo, Japan
ERICA. VANDERWOUDE Cancer Institute, University of Nebraska Medical Center, Omaha, NE, USA
PRISCILLA VELENTGAS Cardiovascular Health Study, University of Washington, Seattle, W A, USA
M. VENDITII Protein and Polypeptide Hormone Laboratory, University of Manitoba, Winnipeg, Canada
FREDERIC M. WALDMAN Department of Laboratory Medicine, University of California - San Francisco, San Francisco, CA, USA
CHERYL LYN WALKER Department of Carcinogenesis, MD Anderson Cancer Center, Smithville, TX, USA
MIAN-YING WANG Department of Biomedical Sciences, UIC College of Medicine, Rockford, IL, USA
KATRINAM. WATERS Department of Biochemistry and Molecular Biology, Mayo Graduate School of Medicine, Rochester, MN, USA
PETER H. WATSON Protein and Polypeptide Hormone Laboratory, University of Manitoba, Winnipeg, Canada
COLIN K.W. WATTS Cancer Research Program, Garvan Institute of Medical Research, st. Vincent's Hospital, Sydney, Australia
Contributors xliii
E. WEIDERPASS Department of Medical Epidemiology, Stockholm, Sweden
NOEL S. WEISS Fred Hutchinson Cancer Research Center, Seattle, W A, USA
ALEsSANDRO WEISZ Instituto di Patologia Generale e Oncologia, Seconda Universita degli Studi di Napoli, Napoli, Italy
DOUGLAS WENDELL Department of Biochemistry, University of Wisconsin, Madison, WI, USA
S. JOHN WEROHA Division of Etiology and Prevention of Hormonal Cancers, University of Kansas Medical Center, Kansas City, KS, USA
ANGELAM. Wn.sON Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA
HEATHER-MARmP. Wn.sON Department of Pathology, University of Washington, Seattle, W A, USA
Y.C. WONG Department of Anatomy, University of Hong Kong, Hong Kong, Peoples Republic of China
B. Xm Department of Anatomy, University of Hong Kong, Hong Kong, Peoples Republic of China
CHUN YANG Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA
JASON YANG Cancer Research Laboratory, University of California, Berkeley, CA, USA
YUTAKA Y ASUI Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Fu-LI Yu Department of Biomedical Sciences, UIC College of Medicine, Rockford, IL, USA
DUJIN ZHOU Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA
