Carcinogenesis: Molecular Hallmarks of Cancer Cells Flashcards
why is the Rb protein a key regulator the the cell cycle.
key regulator by preventing progression from G1 to S phase. negative gene factors inhibit progression of cell cycle by activating Rb protein
what does the inactivation of Rb cause?
this is a common event in tumours and results in resistance to negative growth regulation. (this is the gatekeeper between G1 and S phase of the cell cycle)
how do cancer cells avoid immune destruction?
the tumour cells, bind to the immune checkpoint protein PD-1 and PD-L1 and this inhibits from killing tumour cell
What 2 key events are needed for the transformation from normal to neoplastic cells?
1) Oncogene activation
2) Tumour suppressor gene inactivation
What are caretaker genes?
Genes which maintain genetic stability by repairing damaged DNA and replication errors, controlling the accuracy of mitosis - mutant forms of these genes cause genomic instability
What role do caretaker genes play in carcinogenesis?
Mutations in caretaker genes results in genomic instability - genetic instability is important for enabling specific genetic alterations to accumulate in carcinogenesis
Genetic instability is a common feature of most tumour cells
Why is genetic instability important a common feature of tumour cells?
Just clonal expansion is not enough to aquire the necessary mutations for neoplasm as the normal mutation frequency is not high enough so genetic instability is a key factor
What are the 2 types of tumour suppressor genes?
1) Gatekeepers
2) Caretakers
What are gatekeeper genes?
Genes which play an important role in regulating normal growth
Name 3 types of gatekeeper genes?
1) Negative regulators of the cell cycle and proliferation
2) Positive regulators of apoptosis
3) Positive regulators of cell differentiation
Carcinogens induce molecular abnormalities in tumour suppressor genes which lead to what change in function?
loss of function
What is required for TSG’s to become inactivated?
A first and a second hit - loss of heterozygosity
After the first hit, the single remaining normal copy of TSGs is capable of doing the job of 2 genes - the second hit is required for complete loss of function
The first hit in TSG inactivation is normally what kind of mutations?
a point mutation
The second hit in TSG inactivation is normally one of what 3 types of mutation?
1) Chromosomal non-dysjunction
2) Epigenetic inactivation through promoter methylation
3) Mitotic recombination
What is different about TSGs in people with familial cancer syndromes?
every cell in their body will carry first hit mutations
