Oncotumor - Oncogenes and Tumor Suppressor genes Cancer...

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Oncogenes and Tumor Suppressor genes C ancer arises from the progressive accumulation of genetic lesions Two major classes of mutations: Oncogenes Gain of function Dominant mutation Tumor Suppressor genes Loss of function Recessive mutation Proto-oncogenes Promote normal cell division Onocogenes Mutant forms of proto-oncogenes induce or continue uncontrolled cell division. How were oncogenic mutations discovered? Viral oncogenes (v-onc) Acute transforming retroviruses Induced tumor development in vivo Transformation of cells in vitro Why? Retroviruses insert their DNA into host DNA Viruses took up cellular DNA and changed it Often involved alterations in normal cellular proteins (proto-oncogenes) Identified around 30 oncogenes from retroviral studies C-onc: oncogenes arise by cellular mechanism…not retrovirus DNA transformation was used to identify these sequences
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Proto-oncogenes encode proteins critical in normal cellular growth Activated versions of normal genes Subvert normal signaling pathways Oncogenic conversion found at all levels of signaling cascades including: Cellular component Oncogene Protein Growth factor sis PDGF Β chain Receptor ERBB EGF receptor Cytoplasmic signal molecule RAS G Binding Protein Nuclear transcription factor myc Transcription factor How do oncogenic mutations arise? 5 mechanisms 1. point mutation 2. Gene amplification 3. Chromosomal translocation 4. DNA rearrangement 5. insertional mutagenesis Mechanism 1: point mutation Example:RAS mutation DNA mutation of 1 DNA base Causes change of 1 amino acid
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Can cause protein not to function or function improperly. What is RAS? RAS is a cytoplasmic protein part of the RAS- MAPKinase growth factor signal transduction cascade. Normally, when a growth factor binds to a receptor it activates RAS. RAS is A G-protein
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This note was uploaded on 01/04/2010 for the course BICD BICD100 taught by Professor Smith during the Fall '09 term at UCSD.

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Oncotumor - Oncogenes and Tumor Suppressor genes Cancer...

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