Oncogenic viruses

Question 1

What are 6 features of human cancer cells? What can induce these features?

Answer 1

1. Make tumors if transplanted to animals
2. Undifferentiated
3. Immortal
4. Not contact inhibited
5. Resistant to apoptosis
6. Abnormal chromosomes;
   Virus

Question 2

He gives 7 examples of proto-oncogenes. What were these seven examples and what are they good for?

Answer 2

myc: transcription factor
src: membrane signaling of growth factor binding
ras: signal transduction from surface receptors
sis: PDGF
erb B: growth factor receptor
fms: look at erb B
LMO2: hematopoiesis

Question 3

What two genes are examples of tumor suppressors ie control the cell cycle?

Answer 3

p53 (block G1 to S transition); Rb (prevents E2F from having influence of cell cycle)

Question 4

What oncogenes are overexpressed in some cancers? 6 of them? What is the mechanism(s)?

Answer 4

1. AML: mos
2. CML: abl
3. APL: fes
4. ALL: LMO2
5. Ovarian cancer: myb
6. Breast cancer: her-2/neu;
   amplification, mutation, or translocation

Question 5

What gene(s) is/are often mutated in cancer? Give 7 examples of the cancers?

Answer 5

p53 and Rb; breast, bladder, prostate, liver, lungs, skin, colon

Question 6

How can RNA and DNA oncogenic viruses exert their action mechanistically regarding oncogenes?

Answer 6

RNA: carry activated oncogenes or insert promoter and activate oncogene;
DNA: degrade cell cycle genes

Question 7

What explains the fact that SV40 can transform both hamster and human cells, but only cause sarcoma in the hamsters?

Answer 7

Oncogenic viruses are species-specific!!

Question 8

What exactly in the SV40 genome causes the cancer in hamsters? How does it work mechanistically?

Answer 8

LARGE T ANTIGEN!! It binds p53 and Rb and allows tumor to grow

Question 9

What is an example of an oncogenic virus that causes cancer to newborn rodents but no humans?

Answer 9

Adenoviruses (E1A and E1B, which are analogous to large T antigen and are always expressed in transformed cells)

Question 10

Give an example of non-species specificity among gene therapy viruses?

Answer 10

Mouse leukemia virus modified to transduse stem cells, but some kids developed T cell leukemia because of virus inserting adjacent to LMO2 oncogene

Question 11

Give examples of animal cancers caused by viruses (3)

Answer 11

Sarcoma (sarcoma viruses of cats, chickens, rodents);
Breast cancer (mammary tumor virus of mice);
Leukemia (feline leukemia virus)

Question 12

What is HPV related to? What do low risk subtypes lead to? Intermediate? High risk?

Answer 12

SV40; warts (4, 6, 8); laryngeal papillomas (11); cervical, pharyngeal cancer (16, 18)

Question 13

In HPV, what suppresses E6 and E7? If not suppressed, what do these two do individually and for the cells in general? What if you introduce ras? In low-risk HPV, what is different about E6 and E7?

Answer 13

E2; E6 binds p53 (degradation via ubiquitin pathway) and E7 binds non-P Rb (prevent interaction with E2F); you get immortalization on their own, transformation with mutated ras!!!
lower affinity binding

Question 14

In early stages of HPV, where is HPV genome found relative to human genome? What happens in later stages?

Answer 14

E2 is episomal; if it’s cut in half, it can integrate into genome to allow over-expression of E6 and E7

Question 15

E6 and E7 proteins are expressed _______; around what stage of cervical cancer would HPV DNA integrate?

Answer 15

Continually; CIN III

Question 16

What does EBV cause in western world? Where would we look for nasopharyngeal cancer to show up? Burkitt Lymphoma?

Answer 16

Mono; China; Africa

Question 17

Who does Burkitt affect in particular? At what site? What does the cancer contain and what is going on with the genes?

Answer 17

Pre-pubertal African boys; maxilla; contains EBV and genes are expressed continually

Question 18

For naso-pharyngeal cancer, where is it endemic? What other co-factors are involved? What predicts tumors/recurrence?

Answer 18

South China, Vietnam, Arctic Eskimo; could be food derivatives in China, malaria in Africa; IgA Ab’s to EBV capsid antigen

Question 19

At the chromosomal level, what’s going on with EBV?

Answer 19

Translocation of myc oncogene to promoter of IgH (t8;14), that would be on most of the time since B cells are working

Question 20

Most B cell lymphomas are ______ ______; who would you see this in? Can it regress?

Answer 20

EBV-negative; AIDs patients or long-term immunosuppression; yes if immune function is restored

Question 21

Regarding liver cancer, what do the tumor cells contain? What was the one gene he mentioned that’s involved in potential tumorigenesis?

Answer 21

Integrated HBV;

virus gene x (with ras?)

Question 22

Is hepatits B virus pretective against HCC?

Answer 22

YES!!!

Question 23

When you think of HTLV, where are we thinking? Where would we find HTLV-1 found? Which gene expression is decreased?

Answer 23

Central America in particular, also South America and Africa; integrated into genome of all leukemic cells; Tax

Question 24

When would you see Kaposi’s Sarcoma? Where is it seen predominantly and what do the tumors contain?

Answer 24

Patient that has HIV and HHV-8;

50% carrier rate of KSHV in Africa, 10% in Eastern Europe, contains KSHV DNA and expresses KSVH proteins

Question 25

How does the course of HCC proceed (2 things)?

Answer 25

Over the long haul, with antigens present homozygous (HBsAg+, HBeAg+)