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
how does p14ARF aid in stabilizing p53 and having apoptosis?
MDM2 usually binds to p53 and gets it killed. when p14ARF is activated it secuesters and binds to ALL the MDM2 so they cant bind to p53
what makes p53 unstable and when is it stable?
p53 protein doesnt have a teritary structure until it is bound to DNA target genes
what is the difference between an oncogene and a protooncogene?
oncogene is a gene that causes cancer when it is activated.
a protooncogene is a gene tht can turn into an oncogene if it is mutated
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
what role does tuberosclerosis play in the mTOR pathway and working like a oncogene/tumor supressor?
TSC is usually out there shutting down the action of mTOR which is usually leading to cell growth. TSC is an oncogene because if you shut it down, then you are mTOR gets to run free and overcell growth leads to cancer
what is c-myc and what are c-myc levels in a tumor?
c-myc is a transcription factor that promotes expression of about 15% of human genes. the number of c-myc copies are usually seen at high levels in tumors
what are c-myc levels in regular chromosomes vs. in the HSR region?
in a regular chromosome there is just two dots of c-myc in a HSR region there is a arge area of c-myc called homogenous staining region in FISH
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
what types of mutations makes ras an oncogene?
substitution of glycine at position 12 and 16 prevents ras-GTP from being transformed to ras-GDP so it spends most of its time inactive state
what is the theory behind oncogene addiction and how can it be used in cancer thearpies
tumors get addicted to a a dominat oncogene pathway that could be targeted by drugs and treated
