L30 Cancer Pathobiology 2 Flashcards
How is Ras1 turned on and off?
RAS1 functions as a molecular switches, cycling between an active (GTP- bound) and inactive (GDP- bound) state
What is Ras 1?
RAS 1 is a proto-oncogene, meaning it has the potential to become an oncogene (a cancer-causing gene) when mutated
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What is the importance of ras in growth factor-induced growth?
- Cell growth
- Gene expression
- Cell morphology and movement.
How was the existence of tumour suppressor genes proved?
1) Knudson’s “Two- hit hypothesis”
- Study of retinoblastoma, a childhood eye cancer.
Hypothesis: Knudson proposed that RB development required the inactivation of both copies of a tumour suppressor gene
Familial cases - individuals inherited one inactivated copy of the gene and developed multiple tumours
Sporadic cases - individuals inherited 2 inactivated copy of the genes and developed a single tumour in one eye later in childhood
What are tumour suppressor genes?
They’re like the brakes of a car, helping to regulate cell growth and division. Prevent cells from growing uncontrollably
What are the 2 types of retinoblastoma?
Familial retinoblastoma: Children with a family history of RB often developed multiple tumours in both eyes at an early age
Sporadic retinoblastoma: Children with no family history typically developed a single tumour in one eye later in childhood
Why is knudsens hypothesis important?
Provides evidence:
1. for tumour suppressor gene hypothesis
2. that cancer requires loss of both wild-type alleles
3. for the basis of inherited predisposition to cancer (increased risk of developing certain types of cancer due to genetic changes)
What evidence does cytogenetics provide in inherited retinoblastoma?
They provide evidence for a Chr13 deletion.
What are the difference between oncogenes and tumor suppressor genes?
- Effect of mutation:
Activating gain of function in oncogenes and inactivating loss of function in tumor suppresor. - No. of alleles mutated to exert effect:
One in oncogenes and two in Tumour supp genes. - Effect on function of the protein product: Enhanced in oncogenes and reduced in Tum supp genes.
What is tumorogenesis?
Tumorigenesis is the process by which normal cells in the body are transformed into cancer cells.
Can one mutation cause tumorigenesis?
More than one mutation is required for tumorigenesis
What underpins tumour progression?
Successive rounds of random inherited change and natural selection underpins tumour progression
Are cancer cells genetically stable?
No, cancer cells are genetically unstable and is one of the reasons tumor grown relatively slowly.
What are the causes of genetic instability?
Defects in:
* DNA repair pathways
* Correction mechanisms for DNA replication errors.
* Correction mechanisms for DNA segregation errors
How is apoptosis induced in normal cells?
Through cellular stress such as DNA damage.
What factors in context with apoptosis contribute to tumorigenesis?
Incraesed cell division and decreased apoptosis.
How do normal cells respond to cellular stress?
Through one critical signalling pathway, as the stressors increase the likely outcome is apoptosis.
How is intrinsic apoptosis interrupted?
Mutations in p53 and associated pathways disrupt intrinsic apoptosis.
Give an example of a cell cycle checkpoint gene?
p53 is one example of a cell cycle checkpoint gene
In which phase of the cell cycle does the checkpoint genes operate?
Several checkpoint genes operate in the G1 phase.
How does checkpoints contribute to genetic instability?
Loss of checkpoints contribute to genetic instability.
