haun76 - Medical Biochemistry Cancer and Oncogenes Lecture...

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Medical Biochemistry Cancer and Oncogenes Lecture 76
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Oncogenes Oncogenes may alter cellular metabolism and stimulate growth by several mechanisms sis - B chain of PDGF erb -B - truncated EGF receptor ras - small GTPase src - protein-tyrosine kinase c-myc - DNA-binding protein
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Oncogenes Qualitative and quantitative mechanisms for activation of proto-oncogenes to an oncogene
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Oncogenes vs Tumor Suppressor Genes Oncogenes Mutation in one of two alleles sufficient for activity; act dominant to wild-type Gain of function ” of protein that signals cell division Mutation arises in somatic tissue, not inherited Some tissue preference
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Oncogenes vs Tumor Suppressor Genes Tumor Suppressor Genes Mutation in both alleles or a mutation in one followed by loss or reduction to homozygosity in the second Loss of function of a protein Mutation present in germ cell (can be inherited) or somatic cell Strong tissue preference ( e.g., effect of RB1 gene in the retina)
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RB1 , a Tumor Suppressor Gene Retinoblastoma - malignant tumor of retinal neuroblasts (precursor cells of photoreceptor cells in retina) In hereditary cases, first mutation present in germ cell line and second occurs in retinoblasts ( LOH - loss of heterozygosity ) In sporadic (nonhereditary) cases, both mutations occur in retinoblasts No tumor Most people with inherited mutation develop tumors 1 in 30,000 normal people develop tumors
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RB1 , a Tumor Suppressor Gene pRB is a nuclear phosphoprotein During G 0 or G 1 , RB is hypophosphorylated, binds E2F, blocks G 1 /S transition Phosphorylation increases in late G 1 and early S phases, E2F released, transcribes genes required for S phase, cell enters S phase
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RB1 , a Tumor Suppressor Gene A number of viral proteins ( e.g., SV40 large T antigen, adenovirus E1A) can complex with the hypophosphorylated form of RB RB is thus inactive; abolishes negative regulatory effect on cell division Explains increased multiplication by cells transformed by these viruses
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This note was uploaded on 12/24/2011 for the course STEP 1 taught by Professor Dr.aslam during the Fall '11 term at Montgomery College.

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haun76 - Medical Biochemistry Cancer and Oncogenes Lecture...

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