Transcript oncogene
Chapter 20 oncogene, anti-oncogene and growth factor Relationship of oncogene, antioncogene and growth factor §1 Oncogene • Oncogenes are cellular genes that can trigger uncontrolled cell proliferation if their sequence is altered or their expression is incorrectly regulated. • A gene found in viruses or as part of the normal genome that is involved in triggering cancerous characteristics. • Control the cell growth and cell differentiation. • virus oncogene (v-onc) and cellularoncogene (c-onc) or proto-oncogene Virus- oncogene (v-onc) • Genes are in viruses that can cause tumors in vivo and transform the cell in vitro. In 1910, Peyton Rous found the first retrovirus in a chickens filtrated sarcoma. Rous got the Nobel Prize in Physiology and Medicine in 1966. Cellular Oncogene (c-onc) • Genes are in static or low-level expression state in normal cells under the normal situation and play an important role in maintaining the normal function of cells. Category and major product of cellular oncogene 1. src family — tyrosine protein kinase 2. ras familiy — P21（GTPase activity） 3. myc familiy — intranuclear DNA binding protein 4. sis familiy — P28 (similar platelet derived growth factor) 5. myb familiy — intranuclear transcription factor Product and Function of Protooncogene • Extracellular growth factors • Transmembrane growth factor receptors • Intracellular signal transduction proteins • Intranuclear transcription factors Mechanisms of Oncogene Activation • Obtaining promoter or enhancer • Group translocation or chromosome rearrangements • Proto-oncogene amplification • Gene mutation §2 Anti-oncogene Tumor suppressor gene (anti-oncegene) • A gene whose protein products inhibit cell division, thereby preventing uncontrolled cell growth (cancer). • Coding the restrained protein relating to cell cycle control. • When tumor suppressive gene is deleted and mutated, there is an induced occurrence of tumors. • Rb gene and P53 gene. Rb gene • Rb refers to retinoblastoma. • The major function of Rb gene is the regulation of cell cycle procession. Mechanism of action of Rb gene P53 gene • P53 gene encodes the protein which molecular weight is 53. Biologic function of P53 protein • Suppressing cell cycle • Suppressing transformation function of some oncogenes • Monitoring cell DNA damage • Inducing the cell apoptosis §3 Growth Factor Growth Factor • A kind of signal molecules similar with hormones that are secreted by cells and promote cell proliferation and differentiation. familiar human growth factor Factor EGF EPO HGF IFN- γ IGF NGF PDGF TGFα TGFβ VEGF Principal resource Primary function Submaxillary gland, kidney, duodenal gland kidney Placenta Activated TH1 and NK cells Placent, primarily liver, plasm Neur, submaxillary gland Platelets,endothelial cells,placenta Tumor cell, transforming cell, placenta Activated TH1 cells(T-helper) and natural killer(NK) cells Smooth muscle, tumor Mechanism of action of growth factor Binding membrane receptor Binding intracellular receptor Tyrosine kinase activition Intracellular related protein phosphorylated Intranuclear transcription factor activation Producing second messenger Protein kinase activated genetic transcription growth factorreceptorcompou nds activation related gene