Carcinogenesis II

Question 1

Tumor Suppressors

Answer 1

1. APC
2. BRCA1
3. BRCA2

Question 2

APC gene

Answer 2

1. cytoplasmic protein regulating the localization of beta-catenin protein
   - Wnt2 regulates the activation of beta-catenin by regulating the APC
   - beta catenin bound to E cadherin normally in plasma membrane
   - APC degrades unbound beta catenin in cytoplasm if not bound to E cadherin
   - if APC is gone, FAP (familial adenomatous polyposis) in patients, beta catenin goes into nucleus to transcribe oncogene uncontrollably (c-myc gene)
   - Lost APC—> over expression of c-myc gene and cancer due to unregulated beta-catenin activity of transcribing c-myc in nucleus

Question 3

BRCA1

Answer 3

• related to breast and ovarian cancers
• repair damaged DNA
• suppress uncontrolled cell proliferation
• loss of BRCA1 —> many mutations for malignancy
• a scaffold for protein complexes involved in DNA checkpoints
• S phase checkpoint, S2/M checkpoint, homologous recombination( by affecting BRCA2)

Question 4

BRCA2

Answer 4

-Related to breast and ovarian cancer
- repair damaged DNA
- loss of BRCA2–> mutations for malignancy
- homozygous mutation of BRCA2–> cancer
- heterozygous–> rare recombination–> breast cancer
- binds to RAD 51–> S2/M checkpoints,
homologous recombination

Question 5

Why p53 was mistaken to be an oncogene instead of tumor suppressor?

Answer 5

• Dominant negative mutation—> mistake to be known as an oncogene
• mutant gene is dominant to the wild type gene in cellular transformation
• p53 tetramere subunit, and mutant p53 subunit protein binds to wild type p53 subunit and inactivate it.
• prevent wild type from being a good TF
• p53–> tumor suppressor, important cancer predisposing gene

Question 6

p53 as a “guardian of the genome”

Answer 6

• mutant p53 found in 50% of all cancers
• tumor suppressor gene
• missing p53 accumulates mutations in higher rate–> high malignancy
• prevents potentially deleterious mutations

Question 7

cellular function of p53

Answer 7

• TF for expression of gene preventing cells from replicating damaged or foreign DNA
• required for apoptosis when damaged DNA
• cell cycle arrest–> prevent entering S or M phase until the DNA repair

Question 8

oncogenic viruses inactivating both Rb and p53

Answer 8

1. Adenovirus
   - Adenovirus E1B–> inactivate p53
2. HPV (human papiloma virus)
   - HPV E6–> inactivate p53
   - HPV E7–> inactivate Rb protein

major cause of cancer

Question 9

Human papilloma virus (HPV)

Answer 9

oncogenic virus in human by deleting p53 and Rb protein