The Molecular basis of cancer 2

Question 1

What are the 3 types of genes that regulate cancer?

Answer 1

oncogenes, tumour suppressor genes, mismatch repair genes.

Question 2

what are oncogenes?

Answer 2

genes that promote cancer.

Question 3

what are tumour suppressor genes?

Answer 3

genes that act to prevent cancer?

Question 4

what are mismatch repair genes?

Answer 4

genes that repair mutated DNA thus prevent cancer.

Question 5

how many copies of the gene must mutations occur in for oncogenes?

Answer 5

one copy of the mutated gene. dominant.

Question 6

what are proto-oncogenes?

Answer 6

normal cellular genes that promote cell growth and cell division.

Question 7

what are proto-oncogenes important for?

Answer 7

normal cell survival, growth, development and differentiation.

Question 8

what is the relationship between oncogenes and proto-oncogenes?

Answer 8

oncogenes are altered forms of proto-oncogenes that lead to increased activity of these gene products and can cause cancer.

Question 9

What are the 5 major classes of genes of oncogenes?

Answer 9

1. growth factors.
2. growth factor receptors.
3. intracellular signalling proteins.
4. transcription factors.
5. cell cycle control proteins.

Question 10

oncogenic change results in ____ activity?

Answer 10

increased.

Question 11

example of growth factor?

Answer 11

PDGF

Question 12

Example of growth factor receptors?

Answer 12

EGF receptors (erbB)

Question 13

Examples of intracellular signalling proteins?

Answer 13

protein kinases, ras and raf

Question 14

examples of proteins that control cell cycle?

Answer 14

cyclin d

Question 15

example of proteins that affect apoptosis?

Answer 15

bcl-2

Question 16

example of transcription factors?

Answer 16

Myc

Question 17

how many oncogenes are identified?

Answer 17

over 100

Question 18

what are the 3 main ways a proto-oncogene can become an oncogene?

Answer 18

1. activating mutation in DNA coding sequence.
2. gene amplification/
3. chromosomal translocation

Question 19

example of point mutation?

Answer 19

ras gene

Question 20

example of gene amplification?

Answer 20

HER 2

Question 21

example of chromosomal translocation?

Answer 21

Myc

Question 22

are oncogenes recessive or dominant?

Answer 22

dominant.

Question 23

what are tyrosine kinase receptors?

Answer 23

transmembrane spanning receptors - convert the signals of extracellular growth factors.

Question 24

what are the largest group of oncogenes?

Answer 24

tyrosine kinase receptors.

Question 25

what pathways do tyrosine kinase receptors signal through?

Answer 25

Ras/Map.

Question 26

process of tyrosine kinase receptor activation?

Answer 26

1. growth factor bind to ligand binding site on outside. 2. causes conformation change in receptor. 3. 2 catalytic sites on inside of cell are brought together. 4. use atp to cross phosphorylate each other on tyrosine residues. 5. thus phosphate groups are added to tyrosine residues. 6. receptor now becomes active.

Question 27

what happens once the receptor becomes active?

Answer 27

intracellular signalling proteins are recruited to the cell surface, where they bind to phosphate groups, and then become activated. 2. sends cascade of signals down into cell. 3. once signal is sent, the receptor would be dephosphorylated, ligand would detach, and receptor would become inactive again.

Question 28

what are akt and PDK serine threonine kinases active in?

Answer 28

breast and ovarian cancer.

Question 29

what are src non receptor tyrosine kinases active in?

Answer 29

bowel cancer.

Question 30

what happens to tyrosine kinase receptors in cancer cells?

Answer 30

cannot be switched off. they are permanently sending signals to keep the pathways going.

Question 31

What does CML stand for?

Answer 31

Chronic Myelogenous Leukemia.

Question 32

Why is CML unique?

Answer 32

results from one oncogenic mutation

Question 33

what percentage of leukemias is accounted for by CML?

Answer 33

20%.

Question 34

What translocation occurs for cml?

Answer 34

bcr on long arm of chromosome 22 is translocated with abl on long chromosome of 9.

Question 35

What is the name of the translocation?

Answer 35

philadelphia.

Question 36

What type of translocation occurs?

Answer 36

reciprocal.

Question 37

What can you say in terms of the activity of the fusion protein?

Answer 37

increased activity.

Question 38

what is cml characterised by?

Answer 38

proliferation of immature wbc in bone marrow and peripheral circulation.

Question 39

What are potential symptoms of cml?

Answer 39

fatigue and weakness.

Question 40

effects of bcr-abl fusion?

Answer 40

1. altered adhesion. can move and spread better. 2. mitogenic activation. constantly growing. 3. inhibition of apoptosis. don't die so excess of cells.

Question 41

What does STI-571 (Gleevac) do?

Answer 41

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.

Question 42

What do antibodies against receptor tyrosine kinases do?

Answer 42

interrupt kinase activation signalling though neutralisation of ligand. ligand cannot bind to receptor, so no activation occurs.

Question 43

example of antibodies against receptors?

Answer 43

EGFR targeted therapy - HER2

Question 44

What do antiangiogenics do?

Answer 44

stop VEGF and blood supply.