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Molecular Basis of Cancers - midcoastseniorcollege.org€¦ · Molecular Basis of Cancers q...

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Molecular Basis of Cancers q uncontrolled cell division q genetic defect in signaling pathway, transcription factor, DNA repair q usually requires multiple mutations q inherited or environmental
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Page 1: Molecular Basis of Cancers - midcoastseniorcollege.org€¦ · Molecular Basis of Cancers q uncontrolled cell division q genetic defect in signaling pathway, transcription factor,

Molecular Basis of Cancers

q  uncontrolled cell division

q  genetic defect in signaling pathway, transcription factor, DNA repair

q  usually requires multiple mutations q  inherited or environmental

Page 2: Molecular Basis of Cancers - midcoastseniorcollege.org€¦ · Molecular Basis of Cancers q uncontrolled cell division q genetic defect in signaling pathway, transcription factor,

Transformation of Cultured Cells

Page 3: Molecular Basis of Cancers - midcoastseniorcollege.org€¦ · Molecular Basis of Cancers q uncontrolled cell division q genetic defect in signaling pathway, transcription factor,

Oncogenes

q  discovered in tumor causing viruses

q  derived from host genes – proto-oncogenes q  encode growth factors, receptors, signaling molecules, transcription factors q  genetically dominant – mutation of single gene sends “divide signal”

Page 4: Molecular Basis of Cancers - midcoastseniorcollege.org€¦ · Molecular Basis of Cancers q uncontrolled cell division q genetic defect in signaling pathway, transcription factor,

Amplification of Proto-oncogenes

Page 5: Molecular Basis of Cancers - midcoastseniorcollege.org€¦ · Molecular Basis of Cancers q uncontrolled cell division q genetic defect in signaling pathway, transcription factor,

ErbB Oncogene – Mutated EGF Receptor

Cancers of the - breast - stomach - ovaries

Page 6: Molecular Basis of Cancers - midcoastseniorcollege.org€¦ · Molecular Basis of Cancers q uncontrolled cell division q genetic defect in signaling pathway, transcription factor,

Effect of Multiple Oncogenes on Tumor formation in Mice

Page 7: Molecular Basis of Cancers - midcoastseniorcollege.org€¦ · Molecular Basis of Cancers q uncontrolled cell division q genetic defect in signaling pathway, transcription factor,

Tumor Suppressors

q  normally restrain cell growth

q  genetically recessive – require mutation of both genes

q  if inherit one mutant gene – greater risk

q  examples - pRB – retinoblastoma - p53 – >50% all cancers, 90% skin cancers

Page 8: Molecular Basis of Cancers - midcoastseniorcollege.org€¦ · Molecular Basis of Cancers q uncontrolled cell division q genetic defect in signaling pathway, transcription factor,

Function of Tumor Suppressors

Page 9: Molecular Basis of Cancers - midcoastseniorcollege.org€¦ · Molecular Basis of Cancers q uncontrolled cell division q genetic defect in signaling pathway, transcription factor,

Figure 20-30 Molecular Biology of the Cell (© Garland Science 2008)

Development of Retinoblastomas

Page 10: Molecular Basis of Cancers - midcoastseniorcollege.org€¦ · Molecular Basis of Cancers q uncontrolled cell division q genetic defect in signaling pathway, transcription factor,

DNA Repair Genes

Examples: - ATM – kinase that detects DNA damage, activates p53 - XP – xeroderma pigmentosum - BRCA1 – breast cancers

Page 11: Molecular Basis of Cancers - midcoastseniorcollege.org€¦ · Molecular Basis of Cancers q uncontrolled cell division q genetic defect in signaling pathway, transcription factor,

Colorectal Cancer

q  accounts for 10 % of all cancers in US (about 60,000 deaths/yr) - 90% age >55

q  epithelial cells turnover rapidly, derived from stem cells in crypt, migrate up villi, and sloughed into lumen

q  progression from early polyp (small, benign proliferation of stem cells) to metastatic cancer requires 10-12 years

Page 12: Molecular Basis of Cancers - midcoastseniorcollege.org€¦ · Molecular Basis of Cancers q uncontrolled cell division q genetic defect in signaling pathway, transcription factor,

Tumor Progression in Colon Cancer

Page 13: Molecular Basis of Cancers - midcoastseniorcollege.org€¦ · Molecular Basis of Cancers q uncontrolled cell division q genetic defect in signaling pathway, transcription factor,

Alternative Pathways to Colorectal Cancer


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