Neoplasia 3 Flashcards
What do oncogenes do?
Turn up genes that promote growth
What do tumour suppressor genes do?
Turn off genes that slow growth
What are the 4 NORMAL classes of regulatory genes?
Oncogenes
Tumour Suppressor genes
Genes that regulate programmed cell death (i.e apoptosis)
Genes involved in DNA repair
Where is the APC mutation commonly seen?
Colon Cancer (FAP)
What are the 3 key concepts?
Initiation
Progression
Persistance
What is adenoma?
Dysplastic lesion of glandular epithelium
What are the 3 categories of growth receptors?
Receptors with intrinsic tyrosine kinase activity
7 Transmembrane G protein Couple Receptors
receptors without intrinsic tyrosine kinase activity
What is the most commonly mutated photo-oncogene in tumours?
RAS
How does the mutation of RAS lead to unchecked signalling?
Mutations block the hydrolysis of GTP to GDP
Describe Myc?
One of the last points in the sequence.
Its a nuclear transcription factor that promotes growth
Common in lymphoma
Burkett lymphoma t(8;14) - Myc translocation which is diagnostic
Describe PI3K?
Most commonly mutated kinase in cancer.
Describe 7 transmembrane G protein?
G protein coupled receptors are responsible for a wide range of physiological responses
Often targets of pharmacological agents
Can be involved in cancers
Describe non - intrinsic TK receptors?
They can’t autophosphorylate – recruit something else to do it for them
Describe tumour suppressor genes?
They are lots of proteins which can inhibit the cell cycle
They are often prefixed with a ‘p’ like p53 and p16
Describe p53?
It is the most commonly mutated protein across all cancers
Describe what p53 does?
It senses DNA abnormalities at G1 and pauses the cell cycle. It increases levels of p21 which is a CDK inhibitor.
CDK is activated by cyclins.
If the DNA is repaired p53 restarts the cell cycle, if the repair is not possible p53 imitates apoptosis (via the BAX pathway)
What does PTEN do?
Increases transcription of p27.
P27 blocks CDKs and cell cycle progression
Remember CDK are activated by cyclins
Inhibits PI3K/AKT pathway we saw earlier
Without PTEN and therefore p27 cells can proliferate in an uncontrolled fashion
Name some DNA repair genes?
MLH1 MLH2 PMS1 PMS2
What are the BRCA genes?
They are commonly mutated in breast cancers BRCA 1 and 2
Describe BCL2
It is anti-apoptotic
Intrinsic pathway win mitochondria
What chromosome would you find Bcl2?
Chromosome 18
