麻省理工大学：遗传学（Genetics）讲稿_lecture34

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 9○ sperm ○ zygote growth and mitotic differentiation divisions ○○○○○○⑦ 2 meiotic divisions mitotic divisions endoderm ○○○③③③○ 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 ○ o 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 requlation Cytoplasmic Nuclear signa 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 Cytoplasmic Nuclear G-proteins signa proteins Transcription kinases and transduction their targets actors, e.g., proteins Growth MYC JUN. FOS 9 RAS. ABL Factor (RB) 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 ite 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 mages removed due to copyright reasons Please see Figure 1 in Zwick, E, J. Bange and A Ulrich Dimerized receptor Receptor Tyrosine Kinases as Targets for Anticancer Drugs Trends Mo/ 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 Trans￾cription Factors Images removed due to copyright reasons