BIOL 445 Cancer Biology

Dr. Gidi Shemer

Spring 2012

http://www.cancerquest.org/

Dr Andrejs Liepins/Science Photo Library

Dr. Gidi Shemerbishemer@email.unc.edu

http://www.bio.unc.edu/Faculty/Shemer/

Office Wilson Hall G41

Office hoursTue 3:30- 5:00Wed 10:00- 12:00

BIOL 445- Cancer Biology

BIOL 445

445 = 202 + 205- more depth- a scientific/research approach

The course- Introduction and overview- What inputs a cell gets/oncogenes- How cells react to inputs/tumor suppressor genes

This is NOT a med school course

Cell regulatory networks important in cancer cells

Hanahan and Weinberg, Cell 100:57-70 (2000)

BIOL 445

The course- Introduction and overview- What inputs a cell gets/oncogenes- How cells react to inputs/tumor suppressor genes- Cancer at the tissue and body levels- Cancer therapy

BIOL 445TextbookThe Biology of Cancer by Robert Weinberg(also recommended: Natural Obsession by Natalie Angier)

Grading- Exams (28 X 3) = 84- Project = 16

What are you responsible for?- Lectures - Primary literature and assigned readings- YOUR project- literature search and presentation

What Is Cancer?

Cells within a tissue are normally highly organized and tightly regulated

e.g. intestine e.g. skin

CancerCells lose all controls

Can we fight cancer?

2007 Estimated US Cancer Deaths*

ONS=Other nervous system.Source: American Cancer Society, 2007.

Men289,550

Women270,100

26% Lung & bronchus

15% Breast

10% Colon & rectum

6% Pancreas

6% Ovary

4% Leukemia

3% Non-Hodgkin lymphoma

3% Uterine corpus

2% Brain/ONS

2% Liver & intrahepaticbile duct

23% All other sites

Lung & bronchus 31%

Prostate 9%

Colon & rectum 9%

Pancreas 6%

Leukemia 4%

Liver & intrahepatic 4%bile duct

Esophagus 4%

Urinary bladder 3%

Non-Hodgkin 3% lymphoma

Kidney 3%

All other sites 24%

This Lecture

- Properties of cancer cells

- Tumor progression

- Molecular basis of cancer

- What causes cancer?

Cancer: an aberration of normal development

Cancer cells exhibit behaviors found in normal cells during development & differentiation

However, cancer cells behave independently and do not “obey” controls

Most normal cells have a limited potential to divide

senescent cells

Properties of cancer cells

Normal stem cells can divide indefinitely, but under tight control

Self-renewing stem cell

Differentiated cells

Cancer cells are "immortalized”,just like stem cells, but w/o control

Self-renewing stem cell

Differentiated cells

Cancer cell

Cancer cells do not differentiate

tumor

Normal cells may undergo apoptosis

as part of a developmental program

when cells become “dangerous” (e.g. DNA

damage)

Cancer cells escape apoptosis

blue cells = breast cancer cells

yellow cells = apoptotic cells

Dave McCarthy and Annie Cavanagh

Cancer cells are invasive

Figure 20-17 Molecular Biology of the Cell (© Garland Science 2008)

normal tissue

invasive tumor

Normal cells can be invasive at the right time and place

- Cancer cells do not form differentiated tissues

- Cancer cells are "immortalized”

- Cancer cells are invasive

Major Properties of Cancer Cells

- Cancer cells escape apoptosis

Cancer: an Aberration of Normal Development

Cancer cells exhibit behaviors found in normal cells during development & differentiation

However, cancer cells behave independently and do not “obey” different controls

This Lecture

- Properties of cancer cells

- Tumor progression

- What causes cancer?

- Molecular genetics of cancer

Types of Cancers

Epithelial cells: carcinomas 80-90%Connective tissues: sarcomas 1%Blood and lymphatic systems: leukemias, lymphomas Neuronal system: neuroblastoma, retinoblastoma, etc.

Epithelial cells

Connective tissue

Muscle tissue

Naming Cancers

Prefix Meaning

adeno- gland

chondro- cartilage

erythro- red blood cell

hemangio- blood vessels

hepato- liver

lipo- fat

lympho- lymphocyte

melano- pigment cell

myelo- bone marrow

myo- muscle

osteo- bone

Cancer develops through gradual changesin cell morphology and properties

Tumor = abnormal growth of solid tissue

Figure 20-9 Molecular Biology of the Cell (© Garland Science 2008)

Cancer develops through gradual changesin cell morphology and properties

Cellular changes required for metastasis

Figure 20-44 Molecular Biology of the Cell (© Garland Science 2008)

This Lecture

- Properties of cancer cells

- Tumor progression

- What causes cancer?

- Molecular genetics of cancer

Figure 20-9 Molecular Biology of the Cell (© Garland Science 2008)

Cancer develops through gradual changesin cell morphology and properties

One mutation is not enough !!

A process of natural selection

Cancer cells accumulate mutations

Cancer cells accumulate chromosomal abnormalities

Figure 20-13 Molecular Biology of the Cell (© Garland Science 2008)

What types of genes are mutated in cancers?

Two broad categories

OncogenesGain of function mutations

Tumor suppressor genesLoss of function mutations

oncogeneproto-oncogene

A proto-oncogene: a normal cellular gene that can become an oncogene, upon DNA damage

Oncogenes

dominant

recessive

Cancerous mutations in proto-oncogenes are dominant

Figure 20-27 Molecular Biology of the Cell (© Garland Science 2008)

e.g. the transcription factor- myc

Figure 20-27 Molecular Biology of the Cell (© Garland Science 2008)

dominant

recessive

Cancerous mutations in TSGs are recessive

Example p53: the master guardian

Figure 9.8 The Biology of Cancer (© Garland Science 2007)

Mutations in p53 can be found in half of all tumors

Losing both copies of p53:- No cell cycle arrest (over-proliferation)- Angiogenesis- No apoptosis- No DNA repair (more mutations)

This Lecture

- Properties of cancer cells

- Tumor progression

- What causes cancer?

- Molecular genetics of cancer

What Causes Cancer?

- Random mutations (mistakes in the assembly line)

- Inherited mutations (pre-disposition)

- Environmental factors (chemical; physical)

- Viral infections

Cancer : Accumulation of Mutations

The first association between occupation and cancer

Percivall Pott found that chimney sweeps show substantially higher rates of skin cancer

A sad British chimney sweep

British chimney sweeps didn’t do anything about it

Danish chimney sweeps : a daily bath

after work

Result: significantly lower rates of skin cancer amongst Danish chimney sweeps, compared with

British, even a century later

Figure 2.21b The Biology of Cancer (© Garland Science 2007)

Yamagiwa

Yamagiwa took it one step further

Coal tar condensates induced skin carcinoma in rabbits

Chemicals can directly induce cancer

Cancer can be studied in the lab

Figure 20-20b Molecular Biology of the Cell (© Garland Science 2008)

Carcinogens = agents that contribute to the formation of a tumor

Summary

- Cancer cells exhibit behaviors found in normal cells, but cancer cells are not under control

tumor

- Cancer develops through gradual changes in cell properties

- Oncogenes and tumor-suppressor genes are the molecules behind cancer

- Various factors lead to accumulation of DNA damage and eventually to cancer