Genetics of Cancer Lecture 34
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
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 growth and mitotic differentiation divisions 2 meiotic divisions mitotic divisions endoderm colon gametes (eggs or sperm)
Most of the mutations that contribute to cancer occur in somatic cells – but germ line mutations can also contribute egg sper m zygot e endod e r m col o n g rowth an d di ff e rentiation mitotic di visions mitotic di visions 2 m eiotic di visions gam etes (eggs or spe r m)
Most of the mutations that contribute to cancer occur in somatic cells but germ line mutations can also contribute egg sperm zygote growth and germ line mitotic differentiation divisions 2 meiotic divisions mitotic divisions endoderm colon gametes (eggs or sperm)
Most of the mutations that contribute to cancer occur in somatic cells – but germ line mutations can also contribute egg sper m zygot e endod e r m col o n g rowth an d di ff e rentiation mitotic di visions mitotic di visions 2 m eiotic di visions gam etes (eggs or spe r m) ger m line
Signal Transduction and Growth Regulation Nuclear Cytoplasmic signal proteins transduction proteins Growth Factor Genes
Cytoplasmic signal transduction proteins Nuclear proteins Growth Factor Genes Signal Transduction and Growth Regulation
Great Targets for Dominant Acting Oncogenes Secreted Growth factors,e.g.EGF, PDGF Specific Receptors for Growth factors e.g.,RET,EGFR Nuclear Cytoplasmic proteins G-proteins, signal Transcription kinases and transduction factors,e.g., their targets proteins Growth MYC,JUN,FOS e.g..RAS,ABL (RB) Factor Genes
Cytoplasmic signal transduction proteins Nuclear proteins Growth Factor Genes Great 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 Exterior Cytoplasm Transmembrane domain Kinase active Cytoplasmic domain site Figure by MIT OCW
Receptor Tyrosine Kinases (RTKs) Extracellular domain Cytoplasmic domain Exterior Cytoplasm Kinase activ e site Transmembrane domain Figure by MIT OCW
Receptor Tyrosine Kinases (RTKs) Images removed due to copyright reasons
Receptor Tyrosine Kinases (RTKs) Images removed due to copyright reasons
Extracellular Growth factor Engages with and dimerizes specific receptors on cell surface Images removed due to copyright reasons. Please see Figure 1 in Zwick,E.,J.Bange and A.Ullrich. Dimerized Receptor "Receptor Tyrosine Kinases as Targets for Anticancer Drugs." Trends Mol Med.8,no.1 (Jan 2002):17-23. activates cascade of molecular events Machinery for increased cell proliferation is mobilized
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) Images removed due to copyright reasons. Kinases Trans- cription Factors
Receptor Tyrosine Kinases (RTKs) Kinases Transcription Factors Images removed due to copyright reasons