2.7: cancer Flashcards
(causative factors) genetics
defective alleles inherited from parents
increased predispositions to cancer
normal RB gene function
halts cell cycle in absence of growth factors
mutated RB gene
loss or RB activity
allows proliferation in absence of growth factors
normal p53 gene function
prevents cells with dmg DNA from proliferating
mutated p53 gene
damaged cells continue to divide
normal BRCA1, BRCA2 gene function
repair of DNA double strand breaks
mutated BRCA1, BRCA2 gene
inability to repair breaks
increased risk of ovarian and breast cancer
types of chemical carcinogens
tar, EtBr
how do chemical carcinogens cause cancer
- covalent bonds w DNA -> DNA-carcinogen complex
- distorts DNA double helix
- replication errors
- removing nucleotides
- DNA strand breakage
types of ionising radiation
X-rays, gamma rays, UV rays
how does ionising radiation cause cancer
- high energy
- breaks in DNA backbone / formation of pyrimidine dimers
- permanent base change
types of infectious agents
HIV, HPV
how do infectious agents cause cancer
1, integrate genetic material into human DNA
2. days regulation of cell cycle checkpoints
3. uncontrolled proliferation of dmg DNA cells
what is a proto oncogene?
genes coding for proteins that
promote normal cell growth and division
what is a tumour suppressor gene?
genes coding for proteins that
normally inhibit cell division
cell cycle arrest, DNA repair, blocking angiogenesis and apoptosis
what is a gain in function mutation
proto-oncogene -> oncogene
- increase in amt of protein produced
- hyperactivity of protein
eg Ras gene
how many alleles needed to undergo GOF mutation
1
loss in function mutation
- accumulation of mutations
- excessive cell growth and divisions
eg p53 gene
how many alleles need to undergo LOF mutation
2
why is it relatively difficult to develop cancer?
- proofreading mechanisms check and repair mutations
- cells w irreparable mutation undergo apoptosis via p53
- only mutations in PO or TSG will lead to cancer
- all mutations must occur in a single cell for cancer to form
what is the multi step model of cancer?
- GIF of PO
- LOF of TSG
- evasion of apoptosis
- activation of telomerase gene
- angiogenesis
- metastasis and tissue invasion
activation of telomerase
- cancer cells activate
- add new copies of telomeric repeat seq
- telomeres do not shorten
- cells divide infinitely
limitless replicative potential
what is angiogenesis
formation of blood vessels
supplies nutrients to cancer cells
remove toxic waste
blood vessels provide a route to the rest of the body for metastasis
describe how dysregulation of checkpoints of cell div may result in cancer
- M checkpoint dysregulation
- cells enter anaphase despite improper attachment of spindle fibres of chromosomes at metaphase
- non-disjunction -> daughter cells with extra copies of proto-oncogenes - G1/G2 checkpoint dysregulation
- unrepaired dmg DNA being passed on to daughter cells
dysregulation allows cells w improper structures to enter next cell cycle phase
replicate = uncontrolled and excessive cell division = cancer
