Flashcards in Carcinogenesis : molecular hallmarks of cancer cells Deck (25):
What 2 events need to happen in order for neoplasia to occur?
1) Oncogene activation
2) Tumour Suppressor gene inactivation
What are caretaker genes
are a type of tumour suppressor gene. they maintain genetic stability by repairing damaged DNA and replication errors
What genes maintain genetic stability by repairing damaged DNA and replication errors
What happens when caretaker genes are inactivated?
a higher rate of mutations than normal >>>greater risk of cancer
What are gatekeeper genes?
Gatekeeper are a type of Tumour Suppressor genes play an important role in regulating normal growth.
- negative regulator of cell cycle and proliferation
-positive regulator of apoptosis.
-Positive regulators of cell differentiation.
What is the effect of carcinogens on Tumour suppressor genes?
Loss of function of TSGs
What is 2nd hit inactivation of TSG?
The 1st hit in TSG inactivation usually doesn't have an effect because of the remaining normal copy.
2nd hit of the TSG results in complete loss of function,
Name some TSGs and familial cancer syndromes
-Familial adenomatoud polyposis
-familial breast cancer
-Hereditary non polyposis colorectal cancer
What genes promote cell proliferation, survival, angiogenesis and negative regulation of apoptosis?
What gene mutations leads to activated versions of protooncogenes and gain of function?
cause increased levels of cell proliferation, survival, angiogenesis and inhibition of apoptosis
How many copies of the oncogene need to be activated in order to induce a gain of function?
(the mutated gene is dominant to the other normal parental gene)
What are the mechanisms of oncogene activation?
(of a proto-oncogene from a low transcriptionally active site to an active site leads to increased expression of the oncogene)
(substitution of a single base pair can alter an amino acid in the protein causing it to become hyperactive)
(by insertion of multiple copies of the oncogene leads to increased expression.)
Why are tumour cells said to be self sufficient in growth signals?
Normal cells require signalling by growth factors before they proliferate.
Tumours have the ability to grow in the absence of growth factors.
What is the association between tumour cells and antigrowth signals/
In normal cells cell division will stop in response to negative growth factors and leave the cell cycle.
Tumour cells do not respond to these antigrowth signals so continue to proliferate.
What is the significance of the RB gene in tumour cells?
The RB gene regulate the cell cycle.
In tumours the RB gene is inactivated so leads to resistance in negative growth factor regulation.
What do tumour cells express that makes them immortal?
Telemorase replaces the lost material in DNA. This allows the cell to become immortal.
What is the association between tumours and apoptosis?
normal cells apoptose in abnormal stress / growth.
tumour cells lose the ability to apoptose.
What gene induces apoptosis?
TP53 induces cell cycle arrest to allow repair of DNA damage.
TP53 also induces apoptosis if too much damage.
in TP53 inactivation there is a loss of the apoptotic response.
What happens when TP53 is inactivated
loss of apoptosis
When is the TP53 mutation inherited?
What mutation is inherited in Li-Fraumeni?
TP53 mutation is inherited in Li-Fraumeni
What is the association between vascular endothelial growth factor and tumours?
Tumours need to stimulate a new blood supply (angiogenesis)
They secrete vascular endothelial growth factor that stimulated the growth of new vessels.
What is the function of E-Cadherin and what is its association with tumours?
E-Cadherin is a adhesion molecue that helps epithelial cells to be held together.
Tumour cells lose E-Cadherin. The cells become motile >>>metastasis.