Molecular Basis of Carcinogenesis III

Question 1

What kind of cancers are high risk strains of HPV associated with?

Answer 1

squamous cell cancer that may arise in cervix, vagina, anus, penis, oropharynx, upper GI tract

Question 2

How were viral oncogenes discovered?

Answer 2

• studying animal tumors and retroviruses
• oncogenic viruses have v-onc gene (some are host proto-oncogenes that have been incorporated into the retroviral genome)

Question 3

How are oncogenic viruses identified?

Answer 3

cellular transformation assays

• tumor formation in animals after administration of the oncogene virus
• transformation of cell morphology and growth regulation of infected cells in vitro
• first retroviral gene identified - Rous Sarcoma Virus (RSV) from chicken sarcoma cells

Question 4

Name four retroviral oncogenes

Answer 4

v-sis - growth factor
v-erb-B - growth factor receptor exhibiting tyrosine specific protein kinase activity
v-abl - similar to c-ABL (found in the BCR-ABL translocation) that is over expressed and induced in some forms of CML
v-myc - transcription factors and associated with cellular proliferation

Question 5

What kind of proteins do retroviral oncogenes encode for?

Answer 5

many products mimic hormones or growth stimulating factors by resembling natural hormones or by affecting the structure of cell surface

Question 6

Proto-oncogene

Answer 6

normal genes involved in cell growth and proliferation or inhibition of apoptosis

Question 7

Oncogenes

Answer 7

genes that have the potential to cause cancer

Question 8

What is a Philadelphia chromosome?

Answer 8

BCR-ABL translocation of chromosomes 9 and 22

Question 9

Philadelphia chromosome is used to diagnose what? How is it identified?

Answer 9

• subtype of Chronic Myeloid Leukemia (CML)

- identified with FISH assay

Question 10

Why would you measure the amplification of N-myc in neuroblastoma?

Answer 10

• prognostic factor -> patients with greater than 10 copies of the gene have much worse survival

Question 11

When would you measure neu?

Answer 11

• neu (HER) proto-oncogene is a major driver of several critical signaling pathways that may lead to cancer (protein receptor tyrosine kinase)
• prognostic, predictive and treatment for breast cancer
• patients with neu have a shorter survival
• improved response to higher doses (without neu alterations have the same survival regardless of dose)

Question 12

Herceptin

Answer 12

• used for over expression/amplification of the protein receptor tyrosine kinase gene HER2 (neu)
• targets neu receptor (chimeric mouse-human antibody)
• challenge - clonal progression

Question 13

Gleevac

Answer 13

• ATP analog of several tyrosine kinases
• useful to treat Philadelphia chromosome positive CML
• competitively binds to the kinase domain, preventing binding of ATP and the tyrosine kinase induced transfer of phosphate to various substrates -> stops cell proliferation

Question 14

DNA tumor viruses target _______ and _______.

Answer 14

retinoblastoma (RB) and p53 proteins