6.11 Transforming cells Flashcards
acute vs weak transforming viruses
acute transforming viruses transform cells quickly at low dose
transforming viruses are
retroviruses
why do acute transforming viruses transform cells better?
they have src region in thir DNA like in ATV –first proposed oncogene
src
rous sarcoma virus - rats
ras
harvey sarcoma virus
myc
maloney sarcoma virus - mice
sis
simian sarcoma virus
fes
feline sarcoma virus
viral oncogenes were found in malignant and normal cells bc
transforming retroviruses evolved by picking up mammalian genes and incorporating them into their genome – picking up a gene that makes the cell immortal makes the virus immortal
human dna fed to mice cells use Ca salt showed
loss of contact in hibition and tumor growth, with greater efficiency each time experiment was repeated with tumor DNA
conclusion of contact inhibition mouse cell experiment
the v-ras gene caused the tumor but there was no virus! This means that the gene was simply a mutated mammalian gene, differing on the 12th AA from glycine to valine
ras is a
signal transduction protein - it is a GTP dependent protein, active when bound to GTP, has intrinsic GTPase activity, inactive when bound to GDP
ras is involved in
many function including cell replication
Ras is held to the membrane by
a farnesy membrane anchor and is linked to a growth factor receptor by a bridging protein
activated ras binds
Raf-1, GAP, and activates the Map kinase path, that activates transcription, that activates the myc gene, leading to cell cycle progression
the G to V mutation in v-ras causes
reduces the GTPase activity so ras is locked in the “on” position –>abnormally active signalling for growth
why was ras the first oncogene discovered by random transfecting of DNA?
Ras is the most common activated oncogene encountered in human tumors. Not the most common gene affected, that’s p53
what is a good drug target against v-rase
the farnesyl membrane anchor – farnesyl transferase inhibitors might take away the capacity for ras to bind the membrane so it won’t be able to effectively transduce the signal
NF-1 tumor suppressor gene
GAP protein that binds to ras before map kinase path activation
Molecular basis of cancer
oncogenes, tumor suppressor genes, apoptosis genes, DNA repair genes
Oncogenes
growth factors, growth factor receptors, signal transduction proteins, nuclear regulatory proteins, cell cycle regulators
Growth factors
sis, hst-1, int-2
GF sis
PDGF overexpression
GF hst-1
FGF overexpression
