lecture34

lecture34 - Genetics of Cancer Lecture 34 Alterations in...

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Unformatted text preview: Genetics of Cancer Lecture 34 Alterations in different kinds of Genes cause Cancer Oncogenes dominant gain-of-function mutations promote cell transformation Tumor suppressor genes recessive, loss-of-function mutations promote cell transformation Mutator genes Usually recessive, loss-of-function mutations that increase spontaneous and environmentally induced mutation rates Most of the mutations that contribute to cancer occur in somatic cells – but germ line mutations can also contribute egg sperm zygote endoderm colon growth and differentiation mitotic divisions mitotic divisions 2 meiotic divisions gametes (eggs or sperm) Most of the mutations that contribute to cancer occur in somatic cells – but germ line mutations can also contribute egg sperm zygote endoderm colon growth and differentiation mitotic divisions mitotic divisions 2 meiotic divisions gametes (eggs or sperm) germ line Cytoplasmic signal transduction proteins Nuclear proteins Growth Factor Genes Signal Transduction and Growth Regulation Cytoplasmic signal transduction proteins Nuclear proteins Growth Factor Genes reat Targets for Dominant Acting Oncogenes Secreted Growth factors, e.g. EGF, PDGF Specific Receptors for Growth factors e.g., RET, EGFR G-proteins, kinases and their targets e.g., RAS, ABL, (RB) Transcription factors, e.g., MYC, JUN, FOS Receptor Tyrosine Kinases (RTKs) Extracellular domain Cytoplasmic domain Exterior Cytoplasm Kinase active site Transmembrane domain Figure by MIT OCW. Receptor Tyrosine Kinases (RTKs) Images removed due to copyright reasons. Extracellular Growth factor Engages with and dimerizes specific receptors on cell surface Dimerized Receptor activates cascade of molecular events Machinery for increased cell proliferation is mobilized Images removed due to copyright reasons. Please see Figure 1 in Zwick, E., J. Bange and A. Ullrich. Trends Mol Med . 8, no.1 (Jan 2002): 17-23. "Receptor Tyrosine Kinases as Targets for Anticancer Drugs." Receptor Tyrosine Kinases (RTKs) Kinases Trans- cription Factors Images removed due to copyright reasons. Constitutive Activation converts RTKs to Dominant Acting Oncogenes Images removed due to copyright reasons....
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lecture34 - Genetics of Cancer Lecture 34 Alterations in...

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