L06-Viruses and human cancer Flashcards
What is the percentage of cancers that are caused by viruses in developing countries and why is it higher than developed countries?
25% In developing countries.
This is because there are worse health care services and a different genetic makeup of population.
What can be done to prevent viruses that cause cancers?
They can vaccinate against these viruses.
How do viruses cause cancer?
They can contribute to the genetic insults to the cells resulting in altered expression of the function of proteins controlling growth and division.
In cancer what are the changes to proto-oncogenes and tumour suppressor genes?
You get a gain of function mutation in proto-oncogenes and a loss of function mutation in tumour suppressor genes.
Name some of the main viruses that cause cancer?
Hepatitis C/B-hepatocellular carcinoma
Human papilloma virus (HPV)
Epstein Barr Virus-Burkitt’s Lymphoma, Hodgkin’s lymphoma
What is the difficulty in establishing causation of viruses in cancer?
Often a long period between initial infection and cancer development.
Not all infected with the virus develop the cancer.
What are KSHV viruses?
They are viruses of the HSV family that cause Kaposi’s sarcoma.
What is Kaposi’s sarcoma?
It is a rare condition that effects Mediterranean men. Presents as reddish blotches on skin. It induces changes in spindle morphology in the endothelial cells. These spindle shaped cells lead to tumours.
What are Koch’s postulates and why are they useful?
They are an organism that are regularly associated with disease so can be used to look at viruses and cancer.
In general how does HPV cause cancer?
It causes gain of function mutations in proto-oncogenes (e.g. HPV E6 and E7)
It causes loss of function of mutations in tumour suppressor genes (e.g. pRB and p53)
What is the normal pRB pathway and what effect does HPV E7 have on this?
Normally E2F (transcription factor) is bound to pRB and transcription is inhibited. When appropriate mitogenic signalling occurs this causes increased levels of cyclin D which binds to CDK4. This phosphorylate pRB which causes to the release E2F. When E7 is present it causes dissociation of pRB from E2F regardless of cyclin levels. This is via binding to pRB and inactivating it so it become dissociated from E2F.
How do E6 and E7 affect p53?
p53 normally increases in response to damaged DNA and this leads to G1 arrest or apoptosis. E6 ad E7 inhibit apoptosis by binding to p53 and degrading it. This can lead to further chromosomal instability and oncogenic mutations.
Summarise the effect of E6 and E7 on cervical cells?
They causes continous cell proliferation through pRB.
Loss of p53 mediated DNA repair pathway.
Accumulation of chromosomal mutations that lead to cancer.
