47. Transformation mechanism of proto-oncogens into oncogeny (point mutation, chromosome translocation).

the cancer gene suppressor and their biochemical function. influence of cancer gene-suppressor on the cellular surface molecule, molecules regulating signal transduction, molecule regulating nuclear transcription. point mutation eg: Ras oncogene -affect Gap induced hydrolysis of GTP -90% of pancreatic adenocarcinoma contain RAS point mutation, also 50% fo thyroid and colon cancer, 30% of myeloid leukemias and lung adenocarcinoma chromosomal translocation -result of overexpression of protooncogene eg:Burkits lymphoma -carry 3 translocation, involv chromosome 8q24 (c-myc gene) -mutation cause juxtaposition of c-myc, since this place close to Ig heavy chain gene, it cause d/o in Ig synthesis eg:myeloid leukemia -translocation btwn chromosome 9 and 22 relocates portion of protooncogenes c-abl to beakpoint cluster (bcr) locus on chromosome 22 cancer gene suppressor (cgs) *stop cell proliferation* since protooncogenes encode protein that promote cell growth, CGS stop cell proloferation effect on: 1) cell surface -invlv (eg: DCC-deleted colon carcinoma) -structure of DCC resembles cell surface molecule that invlv in cell to cell/matrix interaction -no DCC cause alteration in differentiation and proliferation 2)regulating signal transduction eg: NF-1 gene -function of NF-1 protein (neurofibromin) related to signal transduction of ras protein -it encodes GAP (GTPase activating protein) facilitates conversion of active ras to inactive ras 3) regulate nuclear transcription eg: Rb gene (DNA binding protein) -quiscent cells contain active unphosphorylated Rb gene that prevent DNA synthesis by binding to transcriptional factor that initiate cell replication