lecture 13-oncogenes Flashcards
(29 cards)
what are the 2 different types of oncogenes
viral and cellular
how are oncogenes produced by viruses
they capture proto oncogenes and transform them
How were RSVs identified
1)remove sarcoma (mesenchymal cancer) from chicken and break into small pieces
2) filter and inject into young chicken
3) result = sarcoma formed
agent must have been small to fit through filter so must be a virus
how was cell transformation achieved in petri dishes with RSV
chicken embryo fibroblasts infected with RSV showed cancer cell traits eg. foci and similar metabolism to cancer cells
what is cell transformation
conversion of normal cell to cancer cell
what are the 2 possible theories for maintainance of cell transformation with RSV and which one is correct
1) RSV transformed progenitors and all their descendants so virus must be present at all times to maintain
2) RS only transforms progenitor cells, which somehow transmit phenotype to descendants
1 is correct
how was the RSV maintainace of transformed cells shown experimentally
using temp dependant RSV mutant
cells lost their transformed state when temperature wasnt optimum, showing RSVs involvement
what are the properties of transformed cells
altered morphology
loss of contact inhibition
anchorage independence
cant die
no GF required for growth
high saturation density
increased glucose uptake
tumorigenicity
which gene/s are responsible for viral replication
gag
pol
env
which gene/s are responsible for transformation in viral oncogenes
src
why arent gag, pol and env responsible for the RSV infection phenotype
they are just responsible for the replication of the virus, not the infection
what is the difference between c-src and v-src
c-src is proto oncogene found in normal genome of vertebrates
v-src is oncogene formed by virus
how were cellular oncogenes identified
chemically transform mouse fibroblasts into cancer cells
DNA extracted and growth on normal mouse fibroblasts
when injected into host -> tumor formed
how many genes are responsible for each cellular oncogene
1
describe normal ras function
Activation: growth factor binds a receptor (like EGFR), it triggers Ras to exchange GDP for GTP.
Active form: Ras-GTP binds and activates downstream effectors (e.g., Raf, PI3K).
Signal cascade: This leads to activation of pathways like MAPK/ERK, promoting cell division, differentiation, or survival.
Inactivation: Ras hydrolyzes GTP → GDP (via intrinsic GTPase activity), turning itself off.
what happens to the ras pathway when no gfs are present
GDP is bound so ras is OFF
what happens in oncogenic ras
no GF bound
GTP always bound
continuous proliferation
what are the three types of ras
H-ras
K-ras
N-ras
how was molecular cloning used to discover the ras mutation which forms oncogenes
cloned proto onco gene and cloned oncogene were transfected into fibroblasts and then foci detection occured
kept testing different fragments to see which part of the sequence was repsonsible for the transformation
mutation was G12V
what is the most common mutation in ras
KRAS g12c
what is AMG510 and what does it do
KRAS inhibitor
forms covalent bond with the GDP- bound KRAS g12c
this prevents GTP binding so decreases signalling
describe the patient results of using AMG510
promising results alone and with chemotherapy
NOT effective in mice lacking an immune system
Why is AMG 510 not effective in mice lacking an immune system?
part of AMG 510’s anti-tumor effect depends on the immune system, particularly T cell–mediated responses.
what occurs when AMG510 is combined with anti-PDI (immunotherapy drug)
increases t cell infiltration
increases pro inflammatory cytokines
