Oncogenic Viruses Flashcards
features of human cancer cells
make tumors if transplanted to animals, undifferentiated, immortal, not contact inhibited, resistant to apoptosis, abnormal chromosomes. all of these features can be induced experimentally by viruses
myc
transcription factor
src
membrane signalling of growth factor binding
ras
signal transduction from surface receptors
sis
platelet-derived growth factor
erb B and fms
growth factor receptor
LMO2
hematopoiesis
what does inactivation of P53 or Rb allow cells to do?
proliferate and accumulate other mutations
how are oncogenes overexpressed in some human cancers?
amplification, mutation, or translocation
P53 is often mutated in what cancers?
breast, bladder, prostate, liver, lung, skin, colon
cell transformation by RNA and DNA viruses
RNA viruses carry activated oncogenes, or insert their promoter and activate an oncogene. DNA oncogenic viruses degrade cell cycle genes
what does T antigen do?
allows cells to proliferate without control. it has to be expressed continually for tumors to grow
E1A and E1B
analogous to T antigen and are always expressed in transformed cells
only example of non-species specificity
gene therapy viruses can have side effects. mouse leukemia virus modified to transduce stem cells. cured cases, but 4/9 developed T cell leukemia due to insertion of virus adjacent to LMO2 oncogene.
oncogenes may have which function in normal cells?
surface receptors for growth factors
human papilloma viruses
related to the SV40 virus. over 100 types. Low risk: 4,6,8 give warts. Intermediate: 11 gives laryngeal papillomas. High risk: 16,18 give cervical and pharyngeal cancer
E6 and E7 in HPV
E6 binds p53 and leads to degradation through the ubiquitination pathway. E7 binds non-phosphorylated Rb, and prevents its interaction with E2F. transfection of cells with E6 and E7 leads to immortalization. co-transfection with mutated ras leads to transformation.
E2 in HPV
E2 normally suppresses E6 and E7. loss of E2 function due to integration allows overexpression of E6 and E7
Epstein-Barr virus
in western world this causes mononucleosis. in-vitro can transform human B cells. prevalent in africa and asia
Burkitt’s lymphoma
endemic in african malaria belt. affects pre-pubertal boys. maxilla most common site. contains EBV and expresses genes continually
naso-pharyngeal cancer
endemic in south china, vietnam, arctic eskimos. contains EBV and expresses genes continually. environmental co-factors involved. IgA antibodies to EBV capsid antigen predicts tumors or recurrences
pathogenesis of EBV-related lymphomas
translocation allows for overexpression of Myc gene, causing cancer
B-cell lymphomas in the western world
most b cell lymphomas are EBV negative. in rare cases, EBV is present and some genes expressed. seen in patients with AIDs or long term immunosupporession (SCID or graft recopients. may regress if immune function is restored
hepatitis B virus
liver cancer incidence is higher in countries with endemic HBV infection. HBV is a risk factor for cancer. prospective studies show greater risk with cirrhosis of liver, or high level expression of viral genes.
