Oncogenes and Onc-Gene Products Folder Title: Oncogene Updated: April 15, 2010 OncTitle Examples of Oncogenic RNA Viruses (from Ruddon, 3rd Ed, Table 6.2) Acute Transforming Viruses Rous Sarcoma (non-defective) Avian Erythroblastosis Avian Myeloblastosis Avian Myelocytomatosis Abelson Leukemia Harvey Sarcoma Kirsten Sarcoma Feline Sarcoma Simian Sarcoma Chicken Sarcoma Chicken Leukemia Chicken Leukemia Chicken Mouse Leukemia Rat Sarcoma Rat Sarcoma Cat Sarcoma Monkey Sarcoma RNAOnc1 Examples of Oncogenic RNA Viruses Acute Transforming Viruses What Genetic Information Makes Them Oncogenic? Rous Sarcoma Avian Erythroblastosis Avian Myeloblastosis Avian Myelocytomatosis Abelson Leukemia Harvey Sarcoma Kirsten Sarcoma Feline Sarcoma Simian Sarcoma Extra Gene src Chicken Sarcoma Chicken Leukemia erb Chicken Leukemia myb myc Chicken abl Mouse Leukemia Rat Sarcoma Ha-ras Rat Sarcoma Ki-ras Cat Sarcoma fms Monkey Sarcoma sis RNAOncG1 Please send in your name under “Send User Data” as Usual I’m here! 1. Yes 2. No 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 56 57 62 63 64 65 66 67 68 69 70 71 72 73 76 77 58 59 0% 60 61 54 55 0% 81 82 83 84 85 86 87 88 89 90 0 of 90 78 o 75 N Y es 74 79 80 Table 4.1 The Biology of Cancer (© Garland Science 2007). P. 100 Cell Site-of-action of Onc-Gene Products (from Scientific American) sis OncLocus Site of Action of Onc-Gene Products Nucleus • myc (N-myc, C-myc, Lmyc) • myb • fos • ski • jun • erb-A Receptor Tyr Kinases • erb-B (EGF Receptor) • erbB-2/neu (her-2/neu) • met • fms • kit • trk Non-receptor Tyr-Kinase • abl • src Ser/Thr Kinases raf PKC (Protein Kinase C) GTP-Binding Proteins Ha-Ras N-Ras K-Ras Growth Factors sis int-2 hst Others B-lym T-lym-1 bcl-1 (Cyclin D1) bcl-2 OncSite Questions About V-Onc Genes Affecting the Biology of Cancer • • • • • • • • • Where Does A Virus Get It From? How Many Different V-Onc Genes Exist? What Protein Does Each Code For? What Do Those Proteins Do? Where Do Those Proteins Do Their Thing? Why Do They Cause Transformation? How Do They Cause Transformation? Do They Have a Normal function? What Do They Tell Us About Neoplastic Transformation Not Involving V-Onc Genes? OncQues1 Alternative Ways in Which Oncogenes Transform Cellular Gene Expression • v-Onc Gene Insertion (Acutely Transforming Retrovirus) • Activation of c-onc Genes (Sub-acutely transforming retroviruses and DNA viruses) • Mutations in c-onc Genes • Gene Rearrangements and Gene Fusions Involving c-Onc Genes • Amplification of c-Onc Genes TransWay Transfection of DNA from Transformed Cells into Normal Mouse Fibroblasts: Figure 4.2 (part 1 of 2) The Biology of Cancer (© Garland Science 2007) p. 96 Determination of Transforming Ability of Transfected DNA Fragments Figure 4.2 (part 2 of 2) The Biology of Cancer (© Garland Science 2007) p. 96 Point Mutation Affecting Amino Acid 12 (Glycine) in H-RAS Gene Product in Human Bladder Cancer Figure 4.10 The Biology of Cancer (© Garland Science 2007) Table 4.2 The Biology of Cancer (© Garland Science 2007) p. 106 In this picture, what is the purple stuff that is being administered to the normal mouse fibroblasts? You can identify it specifically or just generally. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 0 of 90 Amplification of Endogenous c-Oncogene in Human Cancer: N-Myc in Human Neuroblastoma. Figure 4.11b The Biology of Cancer (© Garland Science 2007) p. 107 Table 4.4 The Biology of Cancer (© Garland Science 2007) p. 111 Translocation and Chromosome Fusion in the Activation of Endogeneous C-Oncogenes Figure 4.15a The Biology of Cancer (© Garland Science 2007) p. 113 Fusion Oncoproteins in Human Malignancies; Bcr-Abl Fusion Proteins CNL = Chronic neutrophilic leukemia Figure 4.15b The Biology of Cancer (© Garland Science 2007) p. 113 C-Abl part Table 4.5 The Biology of Cancer (© Garland Science 2007) p. 114 • • • • Questions About c-Onc Genes Affecting Prevention, Diagnosis, and Treatment of Clinical Cancers Can We Prevent Neoplastic Transformation Based on Oncogene Effects? Can We Use Oncogene Expression for Diagnosis and Prognosis? Can We Tailor Existing Treatments Based on Oncogene Expression in a Patient? Can We Develop New Treatments Based on the Biochemistry of Oncogene Products? OncQues2 c-Onc Genes Not Defined by V-Onc Gene Transfection from Viruses c-Onc Genes Perturbed by retrovirus integration int-1 int-2 MLV1-1 MLV1-2 Pim-1 Mouse mammary tumor virus Mouse mammary tumor virus Murine Leukemia Virus Murine Leukemia Virus Murine Leukemia Virus Rat Rat Rat c-Onc Genes Detected by DNA Transfection N-ras Neuroblastoma/leukemia/sarcomas B-lym B-cell lymphoma mam Mammary carcinomas neu Neuroblastoma/glioblastoma cOncFind