Cancer 4 Flashcards
What are the 3 classes of genes implicated in cancer?
(3 marks)
- Proto-oncogene
- Tumour suppressor genes
- Caretaker genes
What do proto-oncogenes do?
(4 marks)
- Promote cell proliferation and cell survival
- Can turn oncogenic
- Gain of function mutation - enhanced normal growth, converts proto-oncogenes to oncogenes
- Only need one copy of gene to have dominant effect and drive cell towards cancer
What happens in cancer when you get a mutation in the coding sequence?
(1 mark)
Protein produced is hyperactive/ permanently active
e.g. Ras is mutated in this way in 70% of human tumours
What happens in gene amplification in cancer?
(2 marks)
- Gene is still normal but too much of normal gene is produced
- e.g. breast cancer get extreme enahancement of Her2 gene which promotes cell proliferation
What happens in chromosome rearrangement in cancer?
(2 marks)
- Rearrangement in chromosome causes a strong promoter nect to a gene that shouldn’t be overexpressed e.g. BCL2 gene overexpressed = antiapoptotic
- Or translocation between 2 chromosomes - fusion gene or protein produced (hyperactive fusion protein) e.g. leukaeimia
What does a mutation in growth inhibitory proteins cause in cancer?
Loss of function - growth is unregulated
In a recessive mutation of growth inhibitory proteins what happens?
(2 marks)
- Loose 2 copies of TS gene before pathological effect is seen e.g. p10, p53 or the retinoblastmoprotein
- This allows cells to grow with damaged DNA and can inhibit more processes
What are the different genetic events that can cause a loss of function of tumour suppressor genes?
(5 marks)
- Loss of whole chromosome
- Regional deletion (containing normal gene)
- Chromosome rearrangement
- Mutation in coding sequence: protein non-functional p10 used to regulate Akt signalling
- p10 dephosphorylates PIP3 which causes PIP2 to shut down Akt signalling
-
Epigenetic changes causing gene silencing
- remodelling complex e.g. SWI/SNF
What are inherited tumour suppresor genes - give an example.
(2 marks)
- Offspring can inherit mutation of one allele of tumour suppresor - has predisposition for tumours e.g. hereditary retinoblastoma: inherited mutation in one allel for RB TS gene (essential for regulating key part of cell cycle)
What is familial adenomatous polyposis (FAP) and Adenomatous polypsis coli (APC)?
(3 marks)
- Loss of tumour suppressor gene (both)
- APC: loss leads to polyps in in epithelial lining of colon
- Patients w/ polyps are monitored and polyps removed regularly
What is a caretaker gene mutation?
(1 mark)
- Cell mutated which leads to an accelerated conversion of normal cell to neoplastic cell
- Loss of function mutation
What do caretaker genes do?
(5 marks)
- DNA repair or prevention of DNA damage
- Different DNA mechanisms for different damages:
- DNA mismatch repair
- Nucleotide excision repair
- Double stranded DNA breaks
What is the name of the inhertied gene that makes you 80-90% more likely to develop breast cancer?
(1 mark)
Braca gene
What intermediate is NOT formed in radiolysis?
(1 mark)
Water
Why may foods act as a cancer causative factor?
(2 marks)
May carry Benzo[a]pyrene - most frequently associated carcinogens with lung cancer
Cooked/ smoked meats
What are cyclin dependent kinases?
(1 mark)
Serine threonine kinases
At what stage in the cell cycle do cyclins appear?
(4 marks)
- Some only in G phase (G1 cyclins)
- Some in late G1 and early S phase (G1/s cyclins)
- Some in S phase (S phase cyclins)
- Some in M phase (M phase cyclins)
What is the main role for CDK activity?
(1 mark)
- Regulating cell cycle events and can be enhanced or inhibited by phsophorylation
How does the cell cycle allow for DNA repair?
(2 marks)
- G2 checkpoint blocks entry into M phase thats incured DNA damage in previous phases or not properly completed S phase
- Allows for DNA repair
How can you regulate CDK?
(4 marks)
- Association with cyclins
- Association with CDK inhbitors
- Addition of phosphate groups that regulate the activity of CDK
- Addition of phosphate groups that inhibit CDK activity
Give a few examples of CDK inhibitors?
(4 marks)
p15, p16, p21 and p27
What are some of the controls put in place to control the cell cycle?
(3 marks)
- Regulated by feedback by processes in that phase
- Checkpoint in mitosis in M phase - checks chromosomes are properly attached to the spindle
- G1 checkpoint - controls transition from G1 phase to S phase
What does tumour suppressor protein RB do?
(3 marks)
- Acts as a molecular link for G1 to S transition
- Prevents cell from going to S phase bound to TF, E2F so no transition past the start
- Inactivation RB promotes chromosomal instability, angiogenesis and increased expression of E2F
What is CDK 4 inhibited by?
(1 mark)
p16
What happens cyclin D is bound to CDK 4?
(2 marks)
- Phosphorylation of RB which then can’t hold onto E2F
- So can go and transcribe genes to push past G1 checkpoints
How does deregulation of cell division and checkpoints occur?
(4 marks)
- Overexpression of proto-oncogene for cyclin D by gene amplification (gene for ti is proto-oncogene)
- Loss of TS genes for p16 CDK inhibitor - due to asbestos exposure
- Loss of TS gene for RB
- Viruses make proteins that affect signalling molecules e.g. HPV makes protein that binds to RB and degrades it
What does p53 do and whath happens when there are mutations to it?
(5 marks)
- Binds to ~300 genes infleunces gene transcription
- Issues in checkpointd p53 are stimulated to produce p26 and p27 - CDK inhibitors put cell in arrest
- In response to radiation, drugs, carcinogen induced DNA damage - puts cell in apoptosis
- Nearly all mutations of p53 found in DNA binding domain
- In low levels of p53, induce antioxidant activity which decreases levels of ROS and subsequent DNA damage
