Molecular Basis of Carcinogenesis III Flashcards
(34 cards)
Retroviruses are
RNA containing membrane enclosed viruses that bud from the cell membrane of infected cells and which usually do not kill the infected cell
The RNA genome consists of
two identical strands held together by a tRNA molecule
The _______ gene codes for internal virion proteins, the _______ gene for virus membrane glycoproteins, and the _______ gene for a virus polymerase
- gag
- env
- pol
When the gag, evn and pol genes are the only ones present, the virus
does not cause tumors, but replicates through an intermediate proviral DNA and integrates into the host cell genome. It can be transmitted as an integrated provirus through somatic or sex cells as a cellular gene
Retroviruses that contain a v-onc segment also have the ability to
rapidly transform appropriate infected cells to the malignant phenotype. They therefore rapidly induce tumors after infection
A few examples of retroviruses that contain a v-onc segment are:
a. nv-src - The oncogene of Rous Sarcoma Virus. This caused fibrosarcomas in certain birds.
b. v-erb - The oncogene of avian erythroblastosis virus causes erythroblastosis in chickens. Two related genes, erb-A and erb-B have been identified.
c. v-abl - The oncogene found in Abelson leukemia virus from mice.
d. v-myc - This gene is usually fused with a portion of the gag gene. It appears that this gene is capable of eliciting neoplastic transformation of cells.
Cellular Transformation is assayed by:
a. Tumor formation in animals after administration of the oncogenic virus.
b. Transformation of cell morphology and growth regulation after infection of cultured cells in vitro. Foci of infected cells developing as transformed clones can be seen and counted
The protein (pp60v-src) coded by the v-src gene is
a membrane bound protein kinase that phosphorylates tyrosine residues in several different proteins. These proteins then change the properties of the cells by affecting gene expression
v-erb-B
codes for a protein that is similar in structure to the cell surface receptor for epidermal growth factor (EGFR). This raises the possibility that this protein has growth stimulating properties like EGFR. This receptor is a member of a family of related proteins that (like pp60v-src) exhibit tyrosine-specific protein kinase activity
v-abl
codes for a protein kinase that phosphorylates tyrosine residues on other proteins. It is similar to the human cellular gene (c-ABL) that is found in the BCR-ABL translocation in the Philadelphia chromosome and is overexpressed in BCR-ABL CML
cellular genes are referred to as c-onc genes. they were also identified by
transfection of DNA from human tumor cells into mammalian cells in culture to produce a malignant phenotype
c-onc genes are involved in _______. Thus, a change in gene regulation or gene structure due to a cellular mutation could _______. Either _______ or _______ in the proto-oncogene are responsible for these effects
- spontaneous malignancies that have nothing to do with a retrovirus
- activate these genes to cause a malignancy
- quantitative changes (too much protein)
- qualitative changes (overactive or unregulated protein)
c-src has a different _______ than v-src and has numerous _______ that do not exist in v-src.
- carboxy-terminal amino acid sequence
- introns
c-myc also has many _______ not present in v-myc, although _______
- introns
- the coding sequences are nearly identical (7 amino acid changes)
A few c-onc genes ligated to _______ can transform normal cells when introduced via DNA mediated transformation (examples: _______).
- retroviral promoters
- c-ras
Analysis of DNA from human bladder cancer cells has shown that _______ genes have been point mutated. Mutations are found in either codon _______ or codon _______ of the gene product. These mutations produce a protein that is _______. Detection of these mutations indicates a _______ prognosis
- c-ras
- 12
- 61
- unregulated and is always “on”
- poor
_______, a member of the _______ family of oncogenes, is found amplified in neuroblastoma. Higher levels of amplification correlate with a _______ prognosis
- N-myc
- c-myc
- poor
The HER2/neu oncogene (also called erbB2), which encodes _______ is amplified in about 20% of _______. Higher levels of amplification correlate with a _______ prognosis
- an integral membrane protein kinase
- breast cancers
- poor
Translocations of _______ genes have been observed in certain human cancers, and also indicate a _______ prognosis. The translocation results in _______
- c-onc
- poor
- inappropriate and high level expression of the oncogene
Drugs have been designed that inhibit _______ that is overexpressed in the BCR-ABL translocation
ABL tyrosine kinase
monoclonal antibodies specific for the protein product of the _______ can reverse the transformed phenotype of the cancer cell
HER2/neu/erbB2 oncogene (Herceptin)
drugs that inhibit _______ are being used to extend the life of breast cancer patients
HER2/neu/erbB2
Injection of the RB gene into a RB-negative small cell lung cancer line will
inhibit tumorigenesis
_______, which cannot inactivate p53 and thereby cannot kill wild-type cells, will kill p53- cancer cells preferentially. A drug has been used to correct the mutant conformation of _______ p53 mutations. This drug blocks the _______ by these p53 mutant cells in a mouse model system.
- E1B mutant adenoviruses
- dominant-negative
- the production of tumors
