cancer module 2- tumour suppressor genes Flashcards
How can tumour suppressor gene mutation induce cancer?
Mutations to the tumour suppressor genes that stop them from working lead to uncontrolled cell proliferation and contribute to cancer.
Explain Alfred knudson’s 2-hit model.
This model explains that in order to induce retinoblastoma, both of the tumour suppressor gene alleles Rb must be mutated.
Hereditary retinoblastoma would be caused by inherting one mutated Rb allele and acquiring a mutation in the second one during life.
Sporadic retinoblastoma would be caused by gaining a mutation in both Rb alleles during life.
Explain haploinsuffiency in the context of tumour suppressor genes.
Haploinsufficiency is when the loss of even one out of two alleles will result in the complete loss of function of that gene. This is the case with tumour suppressor genes.
What are the three types of tumour suppressor genes?
The three types are the tumour suppressor genes are the caretaker, landscaper and gatekeeper genes.
What do caretaker tumour suppressor genes do?
The caretaker TS genes are responsible for maintaining genomic integrity and stability of the cell’s genetic material.
What do gatekeeper tumour suppressor genes do?
These genes are responsible for monitoring and regulating all the stages of the cell cycle whilst the cell is replicating.
What do landscaper tumour suppressor genes do?
These genes are responsible for maintaining a cellular microenvironment that doesn’t promote abnormal cell growth.
In general though, tumour suppressor genes are able to prevent tumour development via which two ways?
TS genes do this by either DNA repair when the genome is damaged or by regulation of the cell cycle during cell division.
What is p53?
p53 is known as the master regulator and gatekeeper of the genome. The initiation of most cancers all involve the mutation of the p53 tumour suppressor gene.
Under what condition do the p53 genes normally operate best?
The p53 genes are activated during times of cellular stress.
What happens to the p53 gene when the cell is in its normal state?
Then the p53 gene is actually inhibited by the mdm family of inhibitors.
How do the mdmx family of proteins inhibit the p53 gene during times of cellular stress?
The mdmX gene inhibits transcription of the p53 gene whilst the mdm2 gene controls the levels of p53 and keeps them low.
Is there a drug that can inhibit the mdmX family from inhibiting p53 to allow increased tumour suppression in the case of cancer?
Yes- this drug is called Nutlin. Nutlin is a mdm inhibitor. Unfortunately, there are many terrible side effects of inhibiting mdm, so the drug is rarely used.
