The Molecular basis of cancer 2 Flashcards
What are the 3 types of genes that regulate cancer?
oncogenes, tumour suppressor genes, mismatch repair genes.
what are oncogenes?
genes that promote cancer.
what are tumour suppressor genes?
genes that act to prevent cancer?
what are mismatch repair genes?
genes that repair mutated DNA thus prevent cancer.
how many copies of the gene must mutations occur in for oncogenes?
one copy of the mutated gene. dominant.
what are proto-oncogenes?
normal cellular genes that promote cell growth and cell division.
what are proto-oncogenes important for?
normal cell survival, growth, development and differentiation.
what is the relationship between oncogenes and proto-oncogenes?
oncogenes are altered forms of proto-oncogenes that lead to increased activity of these gene products and can cause cancer.
What are the 5 major classes of genes of oncogenes?
- growth factors.
- growth factor receptors.
- intracellular signalling proteins.
- transcription factors.
- cell cycle control proteins.
oncogenic change results in ____ activity?
increased.
example of growth factor?
PDGF
Example of growth factor receptors?
EGF receptors (erbB)
Examples of intracellular signalling proteins?
protein kinases, ras and raf
examples of proteins that control cell cycle?
cyclin d
example of proteins that affect apoptosis?
bcl-2
example of transcription factors?
Myc
how many oncogenes are identified?
over 100
what are the 3 main ways a proto-oncogene can become an oncogene?
- activating mutation in DNA coding sequence.
- gene amplification/
- chromosomal translocation
example of point mutation?
ras gene
example of gene amplification?
HER 2
example of chromosomal translocation?
Myc
are oncogenes recessive or dominant?
dominant.
what are tyrosine kinase receptors?
transmembrane spanning receptors - convert the signals of extracellular growth factors.
what are the largest group of oncogenes?
tyrosine kinase receptors.
what pathways do tyrosine kinase receptors signal through?
Ras/Map.
process of tyrosine kinase receptor activation?
- growth factor bind to ligand binding site on outside.
- causes conformation change in receptor.
- 2 catalytic sites on inside of cell are brought together.
- use atp to cross phosphorylate each other on tyrosine residues.
- thus phosphate groups are added to tyrosine residues.
- receptor now becomes active.
what happens once the receptor becomes active?
intracellular signalling proteins are recruited to the cell surface, where they bind to phosphate groups, and then become activated.
- sends cascade of signals down into cell.
- once signal is sent, the receptor would be dephosphorylated, ligand would detach, and receptor would become inactive again.
what are akt and PDK serine threonine kinases active in?
breast and ovarian cancer.
what are src non receptor tyrosine kinases active in?
bowel cancer.
what happens to tyrosine kinase receptors in cancer cells?
cannot be switched off. they are permanently sending signals to keep the pathways going.
What does CML stand for?
Chronic Myelogenous Leukemia.
Why is CML unique?
results from one oncogenic mutation
what percentage of leukemias is accounted for by CML?
20%.
What translocation occurs for cml?
bcr on long arm of chromosome 22 is translocated with abl on long chromosome of 9.
What is the name of the translocation?
philadelphia.
What type of translocation occurs?
reciprocal.
What can you say in terms of the activity of the fusion protein?
increased activity.
what is cml characterised by?
proliferation of immature wbc in bone marrow and peripheral circulation.
What are potential symptoms of cml?
fatigue and weakness.
effects of bcr-abl fusion?
- altered adhesion. can move and spread better.
- mitogenic activation. constantly growing.
- inhibition of apoptosis. don’t die so excess of cells.
What does STI-571 (Gleevac) do?
inhibits activity of abl tyrosine kinase. it is an ATP competitive inhibitor and binds in the place of ATP so the fusion protein is not active.
What do antibodies against receptor tyrosine kinases do?
interrupt kinase activation signalling though neutralisation of ligand. ligand cannot bind to receptor, so no activation occurs.
example of antibodies against receptors?
EGFR targeted therapy - HER2
What do antiangiogenics do?
stop VEGF and blood supply.
