Cancer Flashcards
6 acquired capabilities of cancer cells?
- self-sufficiency in growth signals
- insensitivity to antigrowth signals
- evading apoptosis
- limitless replicative potential
- sustained angiogenesis
- tissue invasion/metastasis
What are 4 ways in which an oncogene can be converted into a protooncogene?
- gene amplification (normal protein overproduced)
- chromosome rearrangement (overproduced)
- deletion or point mutation (hyperactive)
- regulatory mutation (normal protein overproduced)
What are 3 types of oncogenes (5 total)? What type of mutation are result from these?
Dominant in nature due to gain of function mutations
1. Her2 (breast cancer)
ErbB1
- Ras (pancreas, large intestine, biliary cancer)
- C-fos
C-myc (Burkett’s Lymphoma)
C-fos and C-myc are usually unstable, so how does converting them to the protooncogene cause bad things to happen?
they are stabilized and not degraded from the body as quickly and mediate their effects for longer
What are the 3 types of tumor suppressors? What types of mutations cause these?
recessive (two hit)
- Rb: encoded by RB1 gene (retinoblastoma)
- p53: missense mutation in TP53 allele: Li fraumeni
and HPV: E6 binds p53: ubiquination/degradtoin
E7 binds Rb: E2F free to do whatver - Neurofibromatosis: mutation in NF1 which encodes neurofibromin; which functions to accelerate degradation of Ras
What is Li Fraumeni?
heritable condition that greatly increased susceptibility to variety of cancers; due to a mutation in p53
Mutations in p53 lead to what to things?
Li Fraumeni
HPV
What is the active form of p53?
homotetramer
Oncogeneic p53 mutations act as what type of mutations?
dominant negative
What are the 2 things in the caretaker genes section?
- DNA single strand mismatch repair:
MSH2 (mismatch) or MLH1 (repair) genes
leads to HNPCC (lynch syndrome)
- homologus recombination: BRCA1 or BRCA2
HBOC syndrome; can’t repair double stranded breaks
(hereditary breast and ovarian cancer )
How does HNPCC immediate it’s bad effects?
- accumulate microsatellite repeats
- microsatellite instability
- decrease in BAX
- decrease in apoptosis
What does INK4 do?
encodes p16INK4, which encodes inhibition of CDK4/6;
How does suppressing methylation keep CDK 4/6 from being inhibited?
INK4 encodes p16INK which normally inhibit CDK4/6; but they cant do this is methylation is suppressed
How doe telomeres and limitless replicative potential relate to a mutation in p53?
lack of telomere sequences normally activate the breakage/fusion/bridge cycle which would lead to catastrophe and cell death
however, some tumor cells can escape by re-expression of telomerase
How does sustained angiogenesis happen?
- Hypoxia stimulates HIF-1AB
- activates VEGF
- leads to growth of blood vessels
