cancer- matise Flashcards
what does it mean for all cancer cells within a tumor to be clonally related?
it means all tumore begin as a single abnormal cell. but as the cells are dividing, clonal selection might occur and cells from the same clone start differentiating into other cancerous cells
what characteristics of a normal cell do cells lose when they become cancerous?
angiogenesis
ECM interaction
cell adhesion
migration and metastasis
cell division
what is contact inhibition and what happens when cancer cells lose contact inhibition?
in regular cells on a petri dish grow until they contact neighboring cells then they stop. cancer cells dont stop they just keep growing
what are the two tumor supressor genes that can be mutated in a cancer cell?
caretaker genes- repair damaged DNA
gatekeaper genes- restrain cell division and may induce apoptosis
how does Ptch work as a tumore supressor?
by regulating Smo and inhibiting the Hh pathway, it is a way to reduce protein production –>stop cell division. Ptc1 is mutated in meduloblastoma
the two famous gatekeeper genes and caretaker genes
caretaker- BRCA and MLH
gatekeeper- Rb- inhibitsG1/S transition byt inhiiting E2F
p53- initiates apoptosis in response to DNA damage
even though tumor supressor gene mutations are recessive mutations, they appear dominant on a pedigree why?
if one bad copy and one good copy of the gene is inherited, one copy can become inactivated (due to random cellular processes). BUT since tumor cells all arise from only ONE cell in the millions of cells in the body if one of them ends up being the cell with the inactivated good copy, all progeny of that one cell will be cancerous thus it will look like a dominant mutation
what cancer is associated with Nucleotide excision repair and what is the defective gene?
NER: Xeroderma (ERCC1)
Mismatch repair: HPCC colon cancer (MLH gene)
Dounble stranded breaks: breast and ovarian cancer (BRCA)
what is the gene mutated in retinoblastoma and what kind of gene is it?
Rb gene is a gatekeeper gene ehich inhibits entry into G1/S phase and inhibiting E2F
what is the main difference between sporatic and familial retinoblastoma?
familial is usually seen in both eyes vs. sporatic is non heritable and only seen in 1 eye
what is the two hit hypothesis
familial inheritance hits patient sooner than sporatic
what does p53 do?
inhibits cell growth by stimulates transcription of CDK’s.
it is also stimulates transcription of pro apoptotic proteins like Bax
what keeps p53 from not acting until its needed?
p53 is usually unstable in a normal cell. only when the cell is stressed (especially activated by strand breaks) is p53 stablilized and activated
what are the two ways by which p53 can be activated?
- DNA strand breaks that leads to activation of protein kinases. the protein kinases stabilize p53 and activate it.
- growth factors can synthesize p14ARF protein which stabilize p53
p53 is stabilized by and destabilized by. what is p53’s job when its stabilized?
P53 is stabilized by p14ARF and destabilized by MDM2. once P53 is stabilized, it is then able to activate apoptosis.
MDM2 is a survival factor that binds to p53 and gets it degraded so it does not start apoptosis
even though you only need one oncogene to cause an effect, what does it look like on a pedigree?
it looks dominant due to this fact even though it is recessive
how can a NF1 be considered a oncogene?
NF1 usually (a ras-GAP- dephosphorylates ras) is inhibiting ras and shutting down downsteam activities leading to cell growth. if NF1 is shut off, then there is nothing to stop ras and thus you end up with an overactive ras and the too much cell growth
how can a translocation lead to amplicfication of c-myc and Burkitt’s lymphoma?
in this case, a translocation puts an anitbody gene enhancer next to c-myc. thus c-myc is overproduced and you get cancer
in the philadelphia chromosome translocation, what are the two genes that are broght together and what gene is activated?
the bcr and abl gene are usually on different chromosomes but due to the translocation, they are fused and the bcr gene is then activated
