Carcinogenesis III

Question 1

Oncogenes were discovered in ______

Answer 1

certain oncogenic retroviruses.

Question 2

Retroviruses are

Answer 2

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

Question 3

The RNA genome consists of _________

Answer 3

two identical strands held together by a tRNA molecule.

Question 4

The gag gene codes for

Answer 4

internal virion proteins

Question 5

When gag genes are the only ones present, the virus does not ______, but _______.

Answer 5

cause tumors

replicates through an intermediate proviral DNA and integrates into the host cell genome

Question 6

Virus can be transmitted as an _______

Answer 6

integrated provirus through somatic or sex cells as a cellular gene.

Question 7

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

Answer 7

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

Question 8

examples of retrovirus with v-onc segments

Answer 8

1. v-src
2. v-erb
3. v-abl
4. v-myc

Question 9

v-src -

Answer 9

v-src - The oncogene of Rous Sarcoma Virus. This caused fibrosarcomas in certain birds.

Question 10

v-erb

Answer 10

v-erb - The oncogene of avian erythroblastosis virus causes erythroblastosis in chickens. Two related genes, erb-A and erb-B have been identified.

Question 11

v-abl -

Answer 11

v-abl - The oncogene found in Abelson leukemia virus from mice.

Question 12

v-myc -

Answer 12

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 13

Cellular Transformation is assayed by:

Answer 13

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 14

The protein (pp60v-src) coded by the v-src gene is a \_\_\_\_\_\_\_\_\_. 
Theses proteins then change the properties of the cells by affecting \_\_\_\_\_.

Answer 14

membrane bound protein kinase that phosphorylates tyrosine residues in several different proteins.

gene expression

Question 15

v-erb-B codes ________.

Answer 15

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.

Question 16

EGFR receptor is a member of a family of related proteins that _______

Answer 16

(like pp60v-src) exhibit tyrosine-specific protein kinase activity

Question 17

v-abl codes for a _______.

Answer 17

protein kinase that phosphorylates tyrosine residues on other proteins

Question 18

v-able is similar to the human cellular gene (c-ABL) that is found in the______

Answer 18

BCR-ABL translocation in the Philadelphia chromosome and is overexpressed in BCR-ABL CML

Question 19

Many of the products of oncogenes mimic _______

Answer 19

hormones or growth stimulating factors either by resembling natural hormones or by affecting the structure of the cell surface receptors for these hormones

Question 20

oncogene altered receptors then send signals to the ________

Answer 20

cell nucleus in an unregulated manner to affect growth.

Question 21

c-onc genes

Answer 21

Proto-oncogenes

Question 22

Cellular prototypes of the v-onc genes exist in_______ .

Answer 22

all normal eukaryotic cells

Question 23

The proto-onc or c-onc genes are involved in _______

Answer 23

spontaneous malignancies that have nothing to do with a retrovirus.

Question 24

a change in gene regulation or gene structure due to a cellular mutation could _______

Answer 24

activate these genes to cause a malignancy.

quantitative changes (too much protein) or qualitative changes (overactive or unregulated protein) in the proto-oncogene are responsible for these effects.

Question 25

quantitative changes

Answer 25

too much protein

Question 26

qualitative changes

Answer 26

overactive or unregulated protein

Question 27

c-src has a differences from v-src

Answer 27

different carboxy-terminal amino acid sequence and c-src has numerous introns that do not exist in v-src.

Question 28

c-myc differences than v-myc

Answer 28

c-myc also has many introns not present in v-myc, although the coding sequences are nearly identical (7 amino acid changes)

Question 29

if v-onc genes originated from c-onc genes, substantial rearrangements occurred _____

Answer 29

during or after the capture (at least with many such oncogenes).

Question 30

A few c-onc genes ligated to retroviral promoters can _________

Answer 30

transform normal cells when introduced via DNA mediated transformation (examples: c-ras). Other c-onc genes do not directly transform normal cells.

Question 31

c-ras genes have been ______,

Answer 31

point mutated Mutations are found in either codon 12 or codon 61 of the ras gene product.

Question 32

c-ras point mutations produce a _____

Answer 32

ras protein that is unregulated and is always “on”. Detection of these ras mutations indicates a poor prognosis.

Question 33

Gene amplification of c-onc genes has also been detected in some ______.

Answer 33

cancers and is very useful for prognosis.

Question 34

N-myc, a member of the______, and is found ______.

Answer 34

c-myc family of oncogenes amplified in neuroblastoma

Question 35

The HER2/neu oncogene (also called erbB2), which encodes a ________.

Answer 35

integral membrane protein kinase (see v-erb-B) is amplified in about 20% of breast cancers. Higher levels of amplification correlate with a poor prognosis.

Question 36

support for the quantitative model

Answer 36

HER2/neu being amplified in breast cancer

Question 37

support for qualitative model:

Answer 37

c-ras genes being point mutated and always on

Question 38

Translocations of c-onc genes have been observed in certain human cancers, and also indicate ______.

Answer 38

a poor prognosis

Question 39

The translocation results in

Answer 39

inappropriate and high level expression of the oncogene (See Burkitt lymphoma and the Philadelphia chromosome (BCR- ABL translocation)

Question 40

several genes must _________. to transform a normal cell to a malignant one

Answer 40

simultaneously be changed to transform a normal cell to a malignant one. Mutations in both tumor suppressors and oncogenes are needed. The best evidence for this idea has been found in colon cancer.

Question 41

loss of _____ and an increased ______ coupled to loss of _____ can be particularly deadly.

Answer 41

growth regulation mutation rate programmed cell death (apoptosis)

Question 42

In theory, tumor cells may have some of their properties reversed by either _________. This can be accomplished either __________

Answer 42

blocking the action of oncogenes and/or adding back any missing tumor suppressors. at the gene level (gene therapy) or by using drugs or antibodies.

Question 43

monoclonal antibodies specific for the protein product of the HER2/neu/erbB2 oncogene can ______. These antibodies are called _____

Answer 43

HER2/neu/erbB2 oncogene can reverse the transformed phenotype of the cancer cell V

Question 44

drugs that inhibit HER2/neu/erbB2 are being used to ______

Answer 44

extend the life of breast cancer patients. More drugs of this type are currently in clinical trials for both breast and lung cancer.

Question 45

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

Answer 45

tumorigenesis.

Question 46

E1B mutant adenoviruses:

Answer 46

which cannot inactivate p53 and thereby cannot kill wild-type cells, will kill p53- cancer cells preferentially

Question 47

A drug has been used to correct the mutant conformation of dominant-negative p53 mutations . This drug blocks the _______

Answer 47

production of tumors by these p53 mutant cells in a mouse model system.

Question 48

In patients with BCR-ABL translocation, the ABL tyrosine kinase can be inhibited by

Answer 48

Gleevac, an ATP analogue. Clinical trials have shown that Gleevac is effective in 95% of these patients

Question 49

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

Answer 49

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

Question 50

Why do drugs that inhibit “normal” cellular proteins (c-myc, c-abl, etc.) kill only the cancer cells?

Answer 50

One idea is that cancer cells but not normal cells have become dependent or “addicted” to the overexpressed oncogene. This referred to as “oncogene addiction”

Question 51

oncogenes and tumor suppressor genes are being used as “molecular markers” in both ____

Answer 51

cancer diagnosis and prognosis.

Question 52

The elucidation of the function of these genes also will be useful for therapies, either at the gene and/or protein levels and forms the basis of _______

Answer 52

“Personalized Medicine”.

Question 53

_________ is being used for targeted therapy and for “personalized medicine” in cancer.

Answer 53

Molecular knowledge of the genome in cancer cells (Bioinformatics)

Question 54

“heat map” is created in which changes in gene copy number are _____. The “heat map” is created by ___________.

Answer 54

correlated with tumor grade hybridization of the tumor DNA to “gene chip” containing all human genomic DNA sequences as molecular probes

Question 55

Heat map, red color indicates: green indicates:

Answer 55

Red color indicates increases and green indicates decreases.

Question 56

The Breast cancer Xpress ChipTM measures the expression of _____.

Answer 56

123 genes known to be altered in breast cancers This includes tumor suppressors such as BRCA1 and p53 and oncogenes such as estrogen receptor (ER) and erbB2. The information is then used for diagnosis, prognosis and therapy.

Question 57

patients with high erbB2 are treated with _____ and those with high ER levels are treated with ______

Answer 57

Herceptin tamoxifen (estrogen antagonist).

Question 58

With the advent of whole genome sequencing, cancer therapy is being designed _____

Answer 58

on a personal basis depending on the type of mutations (oncogene, tumor suppressor, etc.) in the tumor and the known therapeutic responses to these lesions

Question 59

the env gene codes for

Answer 59

for virus membrane glycoproteins,

Question 60

pol gene codes for

Answer 60

a virus polymerase