slide set 22 Flashcards
driver mutations: 2 broad types of cancer-critical mutations
oncogenes: gain of function mutations
tumor suppressor genes: loss of function mutation
oncogenes
gain of function
cause cell/protein to be overactive
promotes cancer progression!
tumor suppresor genes
loss of funtion mutations
causes protein to not function
Pathway 1: Rb (control cell growth and division)
active Rb is bound to inactive E2F
inactive Rb = phosphorylated
loss of function mutation (tumor suppressor gene)
Pathway 2: Ras (control cell growth and division)
gain of function mutation would cause cancer
over active Ras = activating this pathway more, even when it shouldn’t be
cells would go through the cell cycle that shouldn’t be
PI3K/Akt/mTOR pathway
stimulates growth
- growth factor binds to and activates receptor tyrosine kinases (PI 3-kinase)
- leads to activation of Akt
- leads to mTOR activation
- mTOR increases transport of glucose into cells
- increased glycolysis
- makes more energy, more lipids for cell to grow and divide
gain of function mutations would cause cancer
PI3K/Akt/mTOR pathway also…
inhibits apoptosis
Pathway 3: p53
p53 (control responses to cell stress and DNA damage)
don’t memorize these, just know p53 senses a lot of different
at least 50% of all human cancers have a p53 mutation
(this occurs through loss of function mutation, bc it can’t sense DNA damage, can’t activate transcription of genes that inhibit cell cycle)
Pathway 3: p53
p53 (control responses to cell stress and DNA damage
general pathway overview
oncogene collaboration
we know cells need more than one mutation to override cell safety mechanisms
as mutations accumulate, cancerous phenotypes and cancer occurance can increase
cancer is rare in mice expressing either oncogenic Myc or Ras: need more mutations
cancer cells evolve
driver mutations are aquired and lead to cancer cells
colorectal cancer
shows us steps in tumor progression
identified genes that are highly mutated in colorectal cancer
although the route to full blown cancer progression is not the same for any two cancers,
colorectal cancers often fall into this pattern
don’t memorize image!
just know: cell progresses towards cancerous state before getting there
cells begin to proliferate more, but need more mutations to progress into a carcinoma
ADDITIVE MUTATIONS!
hyperplasia
increase in cell numbers, not cancer yet