Bio_218_gen_basis_cancer_lec_1

Bio_218_gen_basis_ca - How do cellular proto-oncogenes function in human cancer Weinberg's group in 1981 took genomic DNA from carcinogen(coal

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How do cellular proto-oncogenes function in human cancer? Weinberg’s group in 1981 took genomic DNA from carcinogen (coal tar)-induced mouse tumor cells and transfected it into mouse fibroblasts, got transformed cells that generated tumors in mice. DNA from “normal” mouse cells did not form tumors. Suggested that proto- oncogene had been activated in some way… Wigler and Cooper’s groups in 1982 - same experiment, using human cancer cell lines (bladder carcinoma, colon carcinoma) - same result Sequence analysis of transforming bladder carcinoma DNA showed it to be a human homolog of the retroviral Ras oncogene, with a single base pair mutation leading to a single amino acid change ( Ras G12V ). Soon found altered forms of different human proto-oncogenes in tumors, including ras (pancreatic, colon, lung, others), myc (Burkitt’s lymphoma), erbB (stomach, breast, ovarian, brain), Her2/neu (breast)
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What do these proto-oncogene products do? Some important answers have come from a number of different experimental approaches and materials, including C. elegans and Drosophila genetics, biochemistry, and molecular biology Emerging picture - proto-oncogenes encode proteins that control critical regulatory decisions in the signal transduction pathways instructing cells to grow, divide, move, survive, etc. Gain-of-function mutations can activate these pathways in the absence of instructive signals
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Ras pathway components in cancer Ras is a central player – it is found in everything from yeast and humans, and is implicated in important decision making in any organism it’s been studied. Many pathways feed into Ras, and Ras modulates many downstream targets
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This note was uploaded on 06/12/2008 for the course BIO 218 taught by Professor Castronuevo during the Spring '08 term at Drexel.

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Bio_218_gen_basis_ca - How do cellular proto-oncogenes function in human cancer Weinberg's group in 1981 took genomic DNA from carcinogen(coal

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