Rous sarcoma virus(RSv First characterized in 1910 by f. peyton Rous from a chicken tumor later named the rous sarcoma virus mid-1970s, Michael Bishop Harold Varmus(Nobel Prize 1989 ) demonstrated normal animal cells contain non-cancer causing genes(c-Src) closely related to viral oncogenes(v-Src murine leukemia virus terminal repeats -AAA Gag Pol Rous sarcoma virus - AAA A nv host cell DNA tron region encoding kinase domain chicken c-Src proto-oncogene Normal Transformed oncogen pu 20 31 Molecula B elegy of the Ced a/ ie Garand stance ageal Animal fibroblast
◼ Rous sarcoma virus (RSV) - First characterized in 1910 by F. Peyton Rous from a chicken tumor, later named the Rous sarcoma virus; - mid-1970s, Michael Bishop & Harold Varmus (Nobel Prize 1989) demonstrated normal animal cells contain non-cancer causing genes (c-Src) closely related to viral oncogenes(v-Src). Normal Transformed Animal Fibroblast
Cancer arises from malfunction of genes. mutations and or aberrant expression Proto-oncogenes and oncogenes Tumor suppressor genes DNA repair genes
Cancer Arises From Malfunction of Genes: mutations and/or aberrant expression ◼ Proto-oncogenes and oncogenes ◼ Tumor suppressor genes ◼ DNA repair genes
Germline vs, Somatic mutations Germline mutations Somatic mutations Parent child Mutation All cells in Somatic affected In egg or mutation(eg, sperr offspring breast, lung inherited from parents and Are not heritable present in egg or sperm a Occur in specific tissues Cause inherited cancer- Responsible for the majority predisposing syndromes possibly all types of cancers Account for w 5% of all cancers
Germline vs. Somatic mutations Germline mutations Somatic mutations Somatic mutation (eg, breast, lung etc) Mutation in egg or sperm All cells in affected offspring Parent Child ◼ inherited from parents and present in egg or sperm ◼ Cause inherited cancerpredisposing syndromes ◼ Account for ~ 5% of all cancers ◼ Are not heritable ◼ Occur in specific tissues ◼ Responsible for the majority, possibly all, types of cancers
Proto-oncogenes and oncogenes Proto-oncogene: genes which are involved in the promotion of cell division and proliferation in which gain of function mutation can drive a cell toward cancer Oncogenes: mutation, overactive or overexpressed forms of proto-oncogenes. Gain of function dominant at cellular level Normal genes (regulate cell growth) Mutation in one allele (leads to accelerated cell division) Accelerator
Proto-oncogenes and oncogenes ◼ Proto-oncogene: genes which are involved in the promotion of cell division and proliferation, in which gain of function mutation can drive a cell toward cancer; ◼ Oncogenes: mutation, overactive or overexpressed forms of proto-oncogenes. ◼ Gain of function; dominant at cellular level. “Accelerator
Functions of Cellular Proto-Oncogenes 1. Secreted Growth Factors 2. Growth Factor Receptors 4. Nuclear Proteins Transcription 3 Cytoplasmic Factors Signal Transduction Proteins 5. Cell Cycle 6/Anti-apoptosis Genes Genes
4. Nuclear Proteins: Transcription Factors 5. Cell Cycle Genes 3. Cytoplasmic Signal Transduction Proteins 1. Secreted Growth Factors 2. Growth Factor Receptors Functions of Cellular Proto-Oncogenes 6. Anti-apoptosis Genes