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Oncogenes and Onc-Gene Products Folder Title: Oncogene Updated: April 15, 2010 OncTitle.

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Presentation on theme: "Oncogenes and Onc-Gene Products Folder Title: Oncogene Updated: April 15, 2010 OncTitle."— Presentation transcript:

1 Oncogenes and Onc-Gene Products Folder Title: Oncogene Updated: April 15, 2010 OncTitle

2 Examples of Oncogenic RNA Viruses (from Ruddon, 3rd Ed, Table 6.2) Acute Transforming Viruses Rous Sarcoma (non-defective)Chicken Sarcoma Avian Erythroblastosis Chicken Leukemia Avian MyeloblastosisChicken Leukemia Avian MyelocytomatosisChicken Abelson LeukemiaMouse Leukemia Harvey SarcomaRat Sarcoma Kirsten SarcomaRat Sarcoma Feline SarcomaCat Sarcoma Simian SarcomaMonkey Sarcoma RNAOnc1

3 Examples of Oncogenic RNA Viruses Acute Transforming Viruses What Genetic Information Makes Them Oncogenic? Rous Sarcoma Chicken Sarcoma Avian ErythroblastosisChicken Leukemia Avian MyeloblastosisChicken Leukemia Avian MyelocytomatosisChicken Abelson LeukemiaMouse Leukemia Harvey SarcomaRat Sarcoma Kirsten SarcomaRat Sarcoma Feline SarcomaCat Sarcoma Simian SarcomaMonkey Sarcoma Extra Gene src erb myb myc abl Ha-ras Ki-ras fms sis RNAOncG1

4 Please send in your name under “Send User Data” as Usual I’m here! 1.Yes 2.No 0 of 90 1234567891011121314151617181920 2122232425262728293031323334353637383940 4142434445464748495051525354555657585960 6162636465666768697071727374757677787980 81828384858687888990

5 Table 4.1 The Biology of Cancer (© Garland Science 2007). P. 100

6 Cell Site-of-action of Onc-Gene Products (from Scientific American) sis OncLocus

7 Site of Action of Onc-Gene Products Nucleus myc (N-myc, C-myc, L- myc) 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

8 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

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10 Alternative Ways in Which Oncogenes Transform Cellular Gene Expression v-Onc Gene Insertion (Acutely Transforming Retrovirus) Activation of c-onc Genes (Sub-acutely transformingretroviruses and DNA viruses) Mutations in c-onc Genes Gene Rearrangements and Gene Fusions Involving c-Onc Genes Amplification of c-Onc Genes TransWay

11 Figure 4.2 (part 1 of 2) The Biology of Cancer (© Garland Science 2007) p. 96 Transfection of DNA from Transformed Cells into Normal Mouse Fibroblasts:

12 Figure 4.2 (part 2 of 2) The Biology of Cancer (© Garland Science 2007) p. 96 Determination of Transforming Ability of Transfected DNA Fragments

13 Figure 4.10 The Biology of Cancer (© Garland Science 2007) Point Mutation Affecting Amino Acid 12 (Glycine) in H-RAS Gene Product in Human Bladder Cancer

14 Table 4.2 The Biology of Cancer (© Garland Science 2007) p. 106

15 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. 0 of 90 1234567891011121314151617181920 2122232425262728293031323334353637383940 4142434445464748495051525354555657585960 6162636465666768697071727374757677787980 81828384858687888990

16 Figure 4.11b The Biology of Cancer (© Garland Science 2007) p. 107 Amplification of Endogenous c-Oncogene in Human Cancer: N-Myc in Human Neuroblastoma.

17 Table 4.4 The Biology of Cancer (© Garland Science 2007) p. 111

18 Figure 4.15a The Biology of Cancer (© Garland Science 2007) p. 113 Translocation and Chromosome Fusion in the Activation of Endogeneous C-Oncogenes

19 Figure 4.15b The Biology of Cancer (© Garland Science 2007) p. 113 Fusion Oncoproteins in Human Malignancies; Bcr-Abl Fusion Proteins C-Abl part CNL = Chronic neutrophilic leukemia

20 Table 4.5 The Biology of Cancer (© Garland Science 2007) p. 114

21 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

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23 c-Onc Genes Not Defined by V-Onc Gene Transfection from Viruses c-Onc Genes Perturbed by retrovirus integration int-1 Mouse mammary tumor virus int-2 Mouse mammary tumor virus MLV1-1 Murine Leukemia Virus Rat MLV1-2 Murine Leukemia Virus Rat Pim-1 Murine Leukemia Virus 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


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