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
Transformation of Cultured Cells
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”
Amplification of Proto-oncogenes
ErbB Oncogene – Mutated EGF Receptor
Cancers of the - breast - stomach - ovaries
Effect of Multiple Oncogenes on Tumor formation in Mice
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
Function of Tumor Suppressors
Figure 20-30 Molecular Biology of the Cell (© Garland Science 2008)
Development of Retinoblastomas
DNA Repair Genes
Examples: - ATM – kinase that detects DNA damage, activates p53 - XP – xeroderma pigmentosum - BRCA1 – breast cancers
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
Tumor Progression in Colon Cancer
Alternative Pathways to Colorectal Cancer