Chapter 3: Tumor Viruses
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Transcript of Chapter 3: Tumor Viruses
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Chapter 3: Tumor VirusesPeyton Rous discovers a chicken sarcoma virus (1911)
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Rous sarcoma virus is discovered to transform infected cells in culture
Retrovirus
Renato Dulbecco (California IT)
Harry Rubin/ An RSV-induced focus
Howard Temin/ Transformation
Howard Temin, 1975 Nobel Prize with David Baltimore
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Transformed cells forming foci.
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The continued presence of RSV is needed to maintain transformation
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Shope papillomavirusViruses containing DNA molecules are also able to induce cancer
SV40 virus
Permissive hostPolio vaccine (Sabin and Salk) contaminated with SV40 from 1955 to 1963
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Anchorage-independent growth
Nude mice
Tumor viruses induce multiple changes in cell phenotype including acquisition of tumorigenicity
Transformation
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Tumor virus genomes persist in virus-transformed cellsby becoming part of host-cell DNA
Almost all cervical cancer found HPV genome
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The life cycle of an RNA tumor virus like RSV.
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A version of the src gene carried by RSV is also present in uninfected cells
Structure of the RSV genome
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The construction of a src-specific DNA probe.
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RSV exploits a kidnapped cellular gene to transform cells
Proto-oncogene
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The vertebrate genome carries a large group of protooncogenes
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The vertebrate genome carries a large group of protooncogenes
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Slowly transforming retroviruses activate protooncogenesby inserting their genomes adjacent to these cellular genes
Some retroviruses naturally carry oncogenes
Insertional mutagenesis
ALV/ lack acquired oncogenesB-call lymphomas induced by ALV
HTLV-I/ tax (transcription activator)
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Chapter 4: Cellular Oncogenes
Can cancers be triggered by the activation ofendogenous retroviruses?
Transfection of DNA provides a strategy for detecting nonviral oncogenes
Transfection
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Transformation of mouse cells by human tumor DNA
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Oncogenes discovered in human tumor cell lines are related to those carried by transforming retroviruses
Homology between transfected and retroviral oncogenes.
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Amplification of the erbB2/HER2/neu oncogene in breast cancers
Fluorescence in situ hybridization
Kaplan-Meier plot
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Elevated expression of 17q genes together with overexpression of rebB2/HER2
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Nonrandom amplifications and deletions of chromosomal regions
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Proto-oncogenes can be activated by genetic changes affecting either protein expression or structure
Cloning of transfected human oncogenes
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Localization of an oncogene-activating mutant
transfection-focus assay
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Mutation responsible for H-ras oncogene activation
Concentration of point mutations leading to activation of the K-ras oncogene
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Variations on a theme: the myc oncogene can arise via at least three additional distinct mechanisms
N-myc amplification and neuroblastomaGenemycMYC
ProteinMycMYC
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Burkitt’s lymphoma incidence in Africa
Chromosomal translocations in Burkitt’s lymphoma
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Translocations liberating an mRNA from miRNA inhibition
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A diverse array of structural changes in proteins can also lead to oncogene activation
Deregulated firing of growth factor receptors
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Formation of the bcr-abl oncogene
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