Oncogenic viruses Flashcards
What are 6 features of human cancer cells? What can induce these features?
- Make tumors if transplanted to animals
- Undifferentiated
- Immortal
- Not contact inhibited
- Resistant to apoptosis
- Abnormal chromosomes;
Virus
He gives 7 examples of proto-oncogenes. What were these seven examples and what are they good for?
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
What two genes are examples of tumor suppressors ie control the cell cycle?
p53 (block G1 to S transition); Rb (prevents E2F from having influence of cell cycle)
What oncogenes are overexpressed in some cancers? 6 of them? What is the mechanism(s)?
- AML: mos
- CML: abl
- APL: fes
- ALL: LMO2
- Ovarian cancer: myb
- Breast cancer: her-2/neu;
amplification, mutation, or translocation
What gene(s) is/are often mutated in cancer? Give 7 examples of the cancers?
p53 and Rb; breast, bladder, prostate, liver, lungs, skin, colon
How can RNA and DNA oncogenic viruses exert their action mechanistically regarding oncogenes?
RNA: carry activated oncogenes or insert promoter and activate oncogene;
DNA: degrade cell cycle genes
What explains the fact that SV40 can transform both hamster and human cells, but only cause sarcoma in the hamsters?
Oncogenic viruses are species-specific!!
What exactly in the SV40 genome causes the cancer in hamsters? How does it work mechanistically?
LARGE T ANTIGEN!! It binds p53 and Rb and allows tumor to grow
What is an example of an oncogenic virus that causes cancer to newborn rodents but no humans?
Adenoviruses (E1A and E1B, which are analogous to large T antigen and are always expressed in transformed cells)
Give an example of non-species specificity among gene therapy viruses?
Mouse leukemia virus modified to transduse stem cells, but some kids developed T cell leukemia because of virus inserting adjacent to LMO2 oncogene
Give examples of animal cancers caused by viruses (3)
Sarcoma (sarcoma viruses of cats, chickens, rodents);
Breast cancer (mammary tumor virus of mice);
Leukemia (feline leukemia virus)
What is HPV related to? What do low risk subtypes lead to? Intermediate? High risk?
SV40; warts (4, 6, 8); laryngeal papillomas (11); cervical, pharyngeal cancer (16, 18)
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?
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
In early stages of HPV, where is HPV genome found relative to human genome? What happens in later stages?
E2 is episomal; if it’s cut in half, it can integrate into genome to allow over-expression of E6 and E7
E6 and E7 proteins are expressed _______; around what stage of cervical cancer would HPV DNA integrate?
Continually; CIN III
What does EBV cause in western world? Where would we look for nasopharyngeal cancer to show up? Burkitt Lymphoma?
Mono; China; Africa
Who does Burkitt affect in particular? At what site? What does the cancer contain and what is going on with the genes?
Pre-pubertal African boys; maxilla; contains EBV and genes are expressed continually
For naso-pharyngeal cancer, where is it endemic? What other co-factors are involved? What predicts tumors/recurrence?
South China, Vietnam, Arctic Eskimo; could be food derivatives in China, malaria in Africa; IgA Ab’s to EBV capsid antigen
At the chromosomal level, what’s going on with EBV?
Translocation of myc oncogene to promoter of IgH (t8;14), that would be on most of the time since B cells are working
Most B cell lymphomas are ______ ______; who would you see this in? Can it regress?
EBV-negative; AIDs patients or long-term immunosuppression; yes if immune function is restored
Regarding liver cancer, what do the tumor cells contain? What was the one gene he mentioned that’s involved in potential tumorigenesis?
Integrated HBV;
virus gene x (with ras?)
Is hepatits B virus pretective against HCC?
YES!!!
When you think of HTLV, where are we thinking? Where would we find HTLV-1 found? Which gene expression is decreased?
Central America in particular, also South America and Africa; integrated into genome of all leukemic cells; Tax
When would you see Kaposi’s Sarcoma? Where is it seen predominantly and what do the tumors contain?
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
