Oncogenesis Flashcards
Does viral oncogenesis occur with immunosuppression or with chronic inflammation?
Both
how do viruses cause cancer?
indirectly–for hepatitis B and C
directly–papillomavirus
How do viruses directly cause cancer?
DNA viruses can cause cells to enter S phase for their own benefit–but if virus doesn’t complete its life cycle and kill the cell, then viral proteins cause cell to override normal controls on growth
What viruses are associated w human cancer
hepatitis B hepatitis C EBV (herpesvirus) HHV8 (herpesvirus) HTLV1 (lentivirus)-T cell leukemia HPV (papillomavirus)
Where does papillomavirus infect?
cutaneous and mucosal epithelia in hands, feet, anogenital tract
genome of papillomavirus
small
circular
double stranded DNA
Describe HPV early and late genes
early: E1, E2 mediate replication and transcription of viral DNA. E4 helps virus egress. E5,6,7 deal w cellular growth
Late: L1 and L2 make up the capsid
What do E6 and E7 do?
neutralize p53 and Rb, the brakes of the cell cycle
What can a wart formed from HPV infection result in?
resolution, or latency
OR
transformation
Where does HPV initially infect on a tissue level?
basal
Where does virion assembly and release occur for HPV?
in the cornified, apical layers of epithelium
how does HPV change the tissue morphology?
normally, only stratrum basale cells replicate. but HPV stimulates the cell cycle and causes cells in stratum spinosum to replicate–causes cells to be cube shaped still in more apical layers and an overgrowth of tissue
What is the role of Rb protein?
brake that prevents cell from going into S phase.
when there’s enough CDK/cyclin in G1, Rb is phosphorylated and inactivated
What does E7 of HPV do?
Binds to Rb and tags it for degradation
What does p53 do?
activated by inappropriate entry into the cell cycle
causes synthesis of CDK/cyclin inhibitors
stops cell cycle
also can induce apoptosis