Molecular Basis of Carcinogenesis III

Question 1

Retroviruses are

Answer 1

RNA containing membrane enclosed viruses that bud from the cell membrane of infected cells and which usually do not kill the infected cell

Question 2

The RNA genome consists of

Answer 2

two identical strands held together by a tRNA molecule

Question 3

The _______ gene codes for internal virion proteins, the _______ gene for virus membrane glycoproteins, and the _______ gene for a virus polymerase

Answer 3

• gag
• env
• pol

Question 4

When the gag, evn and pol genes are the only ones present, the virus

Answer 4

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

Question 5

Retroviruses that contain a v-onc segment also have the ability to

Answer 5

rapidly transform appropriate infected cells to the malignant phenotype. They therefore rapidly induce tumors after infection

Question 6

A few examples of retroviruses that contain a v-onc segment are:

Answer 6

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.

Question 7

Cellular Transformation is assayed by:

Answer 7

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

Question 8

The protein (pp60v-src) coded by the v-src gene is

Answer 8

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

Question 9

v-erb-B

Answer 9

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

Question 10

v-abl

Answer 10

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

Question 11

cellular genes are referred to as c-onc genes. they were also identified by

Answer 11

transfection of DNA from human tumor cells into mammalian cells in culture to produce a malignant phenotype

Question 12

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

Answer 12

• 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)

Question 13

c-src has a different _______ than v-src and has numerous _______ that do not exist in v-src.

Answer 13

• carboxy-terminal amino acid sequence

- introns

Question 14

c-myc also has many _______ not present in v-myc, although _______

Answer 14

• introns

- the coding sequences are nearly identical (7 amino acid changes)

Question 15

A few c-onc genes ligated to _______ can transform normal cells when introduced via DNA mediated transformation (examples: _______).

Answer 15

• retroviral promoters

- c-ras

Question 16

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

Answer 16

• c-ras
• 12
• 61
• unregulated and is always “on”
• poor

Question 17

_______, a member of the _______ family of oncogenes, is found amplified in neuroblastoma. Higher levels of amplification correlate with a _______ prognosis

Answer 17

• N-myc
• c-myc
• poor

Question 18

The HER2/neu oncogene (also called erbB2), which encodes _______ is amplified in about 20% of _______. Higher levels of amplification correlate with a _______ prognosis

Answer 18

• an integral membrane protein kinase
• breast cancers
• poor

Question 19

Translocations of _______ genes have been observed in certain human cancers, and also indicate a _______ prognosis. The translocation results in _______

Answer 19

• c-onc
• poor
• inappropriate and high level expression of the oncogene

Question 20

Drugs have been designed that inhibit _______ that is overexpressed in the BCR-ABL translocation

Answer 20

ABL tyrosine kinase

Question 21

monoclonal antibodies specific for the protein product of the _______ can reverse the transformed phenotype of the cancer cell

Answer 21

HER2/neu/erbB2 oncogene (Herceptin)

Question 22

drugs that inhibit _______ are being used to extend the life of breast cancer patients

Answer 22

HER2/neu/erbB2

Question 23

Injection of the RB gene into a RB-negative small cell lung cancer line will

Answer 23

inhibit tumorigenesis

Question 24

_______, 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.

Answer 24

• E1B mutant adenoviruses
• dominant-negative
• the production of tumors

Question 25

In patients with _______, the ABL tyrosine kinase can be inhibited by Gleevac (ST1571), an ATP analogue

Answer 25

BCR-ABL translocation (The Philadelphia chromosome)

Question 26

In patients with BCR-ABL translocation (The Philadelphia chromosome), the _______ can be inhibited by Gleevac (ST1571), an ATP analogue

Answer 26

ABL tyrosine kinase

Question 27

In patients with BCR-ABL translocation (The Philadelphia chromosome), the ABL tyrosine kinase can be inhibited by _______, an ATP analogue

Answer 27

Gleevac (ST1571)

Question 28

In patients with BCR-ABL translocation (The Philadelphia chromosome), the ABL tyrosine kinase can be inhibited by Gleevac (ST1571), _______

Answer 28

an ATP analogue

Question 29

“Molecularly targeted therapy” or “rationally designed drug therapy”

Answer 29

identifying the defect in the tumor from the patient and then targeting the therapy to fit it

Question 30

“oncogene addiction”

Answer 30

cancer cells but not normal cells have become dependent or “addicted” to the overexpressed oncogene

Question 31

oncogenes and tumor suppressor genes are being used as _______ in both cancer diagnosis and prognosis. The elucidation of the function of these genes also will be useful for _______, either at the gene and/or protein levels and forms the basis of _______

Answer 31

• “molecular markers”
• therapies
• “Personalized Medicine”.

Question 32

“heat map” is created in which changes in _______ are correlated with _______. The “heat map” is created by _______. Red color indicates _______ and green indicates _______.

Answer 32

• gene copy number
• tumor grade
• hybridization of the tumor DNA to “gene chip” containing all human genomic DNA sequences as molecular probes
• increases
• decreases

Question 33

The Breast cancer Xpress Chip measures _______. This includes tumor suppressors such as _______ and _______ and oncogenes such as _______ and _______. The information is then used for diagnosis, prognosis and therapy.

Answer 33

• the expression of 123 genes known to be altered in breast cancers
• BRCA1
• p53
• estrogen receptor (ER)
• erbB2

Question 34

patients with high erbB2 are treated with _______ and those with high ER levels are treated with _______

Answer 34

• Herceptin

- tamoxifen (estrogen antagonist)