L2 Flashcards
what type of mutation do oncogenes typically have
gain of function
proto-oncogenes
naturally occurring genes in our body that are highly regulated and are used during development and tissue repair
diagnosis vs prognosis
o Diagnosis = what the disease is
o Prognosis = how it will develop over time
Predicting how well the patient will do with treatment options
how many stages of cancer are there
stages 0-4
5 stages total
what are the stages of cancer based on
Size of tumor
Location and spread of tumor
Weight, sex, M/F
patients with non-metastatic tumours have lower levels of what protein
Myc
how can Myc help us predict patient prognosis
- based on a patients MYC level, you can estimate whether their tumor will be metastatic
- Patients with low MYC Level tend to live longer (metastasis-free survival probability)
3 things markers can be predictive of
drug sensitivity
resistance
adverse events
is one oncogene activation sufficient to cause cancer
typically no - we have safety measures built in
how many oncogene activations needed in humans and mice to cause cancer
mice -2
humans -4
does MYC up regulate or repress genes
can do either
overall affect of MYC
cell growth and proliferation - potentiates apoptosis
2 types of molecules that regulate apoptosis
Pro-apoptotic molecules
Anti-apoptotic molecules
examples of anti-apoptotic molecules
MCL-1, BCL-1
examples of pro-apoptotic molecules
BAX-BAK, BH3 only proteins
how do BAX and BAK promote apoptosis
create a pore in mitochondrial membrane - allow for cytochrome C release
what does cytochrome C do once released into cytoplasm
activates caspases
Why is BCL-2 robust
if you have a high level of BCL-2, you won’t have apoptosis
is BCL-2 an oncogene
yes because lots of B-cell lymphomas have BCL-2 over expression
what do you see if you overexposes Myc in REF
little white circles - cells dying due to apoptosis
what happens if you overexposes Myc in primary cells, and what does this indicate
cells have trouble growing because a lot of them die
this indicates that Myc alone cant cause tutors
what molecule does Myc cooperate well with
BCL2
transgenic mice that express Myc alone - result
you might get other spontaneous mutations that help out myc and eventually youll get tumor
transgenic mice expressing Myc and BCL-2 together
right away they get cancer and die
how do BCL-2 and Myc overexpresssion transform cells
probably self sufficiency in growth signals
is ras an oncogene
yes
what happens if you activate ras in primary cells
senescence
what happens if you put Myc and Ras together in a mouse (breast tissue)
promoter called mmtb and only active in breast tissue - you get cancer
Myc alone takes how many days for mice to get cancer
100
ras alone takes how many days for mice to get cancer
40
Myc + ras in mice
majority of mice get cnacer
what do you see in vitro when you overexposes Ras
no more contact inhibition - transformed cells
oncogene defnition
any gene that, when altered in expression pattern or function, contributes to the transformed state of the cell
oncogene mechanism of action
DOMINANT
