Carciongenesis III Flashcards
Discovery of oncogenes
- observing oncogenic retroviruses
- gag gene– internal virion protein
- env gene– virus membrane glycoporoteins
- pol gene– virus polymerase
- - harmless by themselves but replicate and transmitted in the host cell genome through somatic or sex cells - more oncogenes in retroviruses
- v-onc segment–> ability to rapidly transform infected cells to malignant phenotype
- v-src–> oncogene or Rous Sarcoma virus–> fibrosarcomas in birds
- v-erb–> oncogene of avian erythroblastosis virus–> erythrobalstosis in chickens
- v-abl–> oncogene in Abelson leukemia virus from mice
- v-myc–> fused with gag gene, capable of eliciting neoplastic transformations. - cellular transformation check
- assayed by tumor formation in animals after oncogenic virus
- transformation of cell morphology and growth regulation after infection of cultured cells in vitro
- foci of infected cells develop as clones can be counted
viral oncogenes proteins
- pp60v-src by v-src gene
- v-erb-B protein
- v-able protein
- v-able protein
- c-src protein
- c-myc protein
- c-ras
pp60v-src protein
membrane bound protein kinase phosphorylating the tyrosine residues in different proteins, affecting gene expression
v-erb-B protein
- similar structure to receptor for epidermal growth factor (EGFR)
- tyrosine specific protein kinase activity
- growth simulating protein
v-able protein
- protein kinase phosphorylating tyrosine residue on other proteins
- similar to c-ABL in BCR-ABL translocation in Philadelphia chromosome
- over-expressed in BCR-ABL CML(chronic myeloid leukemia)
c-src
- different carboxy terminal aa than v-src
- more introns
c-myc
- many introns more than v-myc, almost identical
substantial rearrangement
c-onc to v-onc
oncogenes as molecular markers in prognosis
oncogenes and tumor suppressors are good markers for cancer diagnosis and prognosis
- oncogene–> amplified
- tumor suppressor–> reduced
example of molecular marker for prognosis (c-ras gene)
detection of c-ras gene
- poor prognosis
- point mutation for human bladder cancer cell
- mutations in codon 12 or codon 61 of the ras gene
- detection of ras mutaiton–> poor diagnosis
- qualitative model (overactive protein)
example of molecular marker for prognosis (amplification of c-onc genes)
amplification of c-onc genes
- poor diagnosis
- n-myc amplification in neuroblastoma
- HER2/neu oncogene amplification about 20% in breast cancer
- quantitative model (too much protein)
- good because targeted drug can be designed
example of molecular marker for prognosis
translocations of c-onc
detection of translocations of c-onc gene
- poor diagnosis
- qualitative model (over expression)
- Burkitt lymphoma
- philadelphia chromosome (BCR-ABL translocation)
- good because targeted drug can be desgined
Def of oncogene
- normally stimulate cellular proliferation
- mutation activates oncogene
Def of tumor suppressor
- normally inhabit cellular proliferation
- mutation deactivates tumor suppressor
oncogene and tumor suppressor contribution to cancers
- both bush mutations
- loss of growth regulation
- increased mutation rate
- loss of apoptosis in colon cancer
