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Chapter 3: Tumor Viruses

Chapter 3: Tumor Viruses. Peyton Rous discovers a chicken sarcoma virus (1911). Rous sarcoma virus is discovered to transform infected cells in culture. Renato Dulbecco (California IT). Harry Rubin/ An RSV-induced focus. Howard Temin/ Transformation.

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Chapter 3: Tumor Viruses

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  1. Chapter 3: Tumor Viruses Peyton Rous discovers a chicken sarcoma virus (1911)

  2. Rous sarcoma virus is discovered to transform infected cells in culture Renato Dulbecco (California IT) Harry Rubin/ An RSV-induced focus Howard Temin/ Transformation Howard Temin, 1975 Nobel Prize with David Baltimore Retrovirus

  3. Transformed cells forming foci.

  4. The continued presence of RSV is needed to maintain transformation

  5. Shopepapillomavirus Viruses containing DNA molecules are also able to induce cancer Permissive host Polio vaccine (Sabin and Salk) contaminated with SV40 from 1955 to 1963 SV40 virus

  6. Tumor viruses induce multiple changes in cell phenotype including acquisition of tumorigenicity Transformation Anchorage-independent growth Nude mice

  7. Tumor virus genomes persist in virus-transformed cells by becoming part of host-cell DNA Almost all cervical cancer found HPV genome

  8. The life cycle of an RNA tumor virus like RSV.

  9. A version of the src gene carried by RSV is also present in uninfected cells Structure of the RSV genome

  10. The construction of a src-specific DNA probe.

  11. RSV exploits a kidnapped cellular gene to transform cells Proto-oncogene

  12. The vertebrate genome carries a large group of protooncogenes

  13. The vertebrate genome carries a large group of protooncogenes

  14. Slowly transforming retroviruses activate protooncogenes by inserting their genomes adjacent to these cellular genes Insertional mutagenesis ALV/ lack acquired oncogenes B-call lymphomas induced by ALV Some retroviruses naturally carry oncogenes HTLV-I/ tax (transcription activator)

  15. Chapter 4: Cellular Oncogenes Can cancers be triggered by the activation of endogenous retroviruses? Transfection Transfection of DNA provides a strategy for detecting nonviraloncogenes

  16. Transformation of mouse cells by human tumor DNA

  17. Oncogenes discovered in human tumor cell lines are related to those carried by transforming retroviruses × Homology between transfected and retroviral oncogenes.

  18. Amplification of the erbB2/HER2/neuoncogene in breast cancers Kaplan-Meier plot Fluorescence in situ hybridization

  19. Elevated expression of 17q genes together with overexpression of rebB2/HER2

  20. Nonrandom amplifications and deletions of chromosomal regions

  21. Proto-oncogenes can be activated by genetic changes affecting either protein expression or structure Cloning of transfected human oncogenes

  22. Localization of an oncogene-activating mutant transfection-focus assay

  23. Mutation responsible for H-rasoncogene activation Concentration of point mutations leading to activation of the K-rasoncogene

  24. Variations on a theme: the myconcogene can arise via at least three additional distinct mechanisms N-mycamplification and neuroblastoma Gene myc MYC Protein Myc MYC

  25. Burkitt’s lymphoma incidence in Africa Chromosomal translocations in Burkitt’s lymphoma

  26. Translocations liberating an mRNA from miRNA inhibition

  27. A diverse array of structural changes in proteins can also lead to oncogene activation Deregulated firing of growth factor receptors

  28. Formation of the bcr-abloncogene

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