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

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