Molecular Mechanisms of Cancer

Question 1

What is Telomerase?

Answer 1

An enzyme which can elongate telomeres

Question 2

Telomerase activity is essential for allowing cells to keep?

Answer 2

Proliferating

Question 3

As cells age, telomerase becomes inactive and hence?

Answer 3

Telomeres shorten the ability to divide – limits lifespan

Question 4

Cell proliferation is regulated by?

Answer 4

Transit through the cell cycle

Question 5

What are the 4 phases of the cell cycle?

Answer 5

1. G1 - cell growth & protein synthesis
2. S-phase - DNA synthesis
3. G2 - Cell gets ready to split
4. M phase - cell splits

Question 6

Transit through cycle regulated by?

Answer 6

Checkpoints

Question 7

Progression through cell cycle checkpoints controlled by?

Answer 7

Cyclin Dependent Cellular (CDKs) and CDK inhibitors

Question 8

What is the role of CDks and the inhibitors?

Answer 8

1. Correct sequence of phases (G1, S, G2, M)
2. Cellular & environmental conditions are favorable
3. DNA is properly replicated & undamaged

Question 9

G1/S transition checkpoint?

Answer 9

Are growth factors present?
Are nutrients available?
Is DNA damaged ?
Is the cell big enough

Question 10

G2/M transition checkpoint?

Answer 10

1. Has DNA replicated
2. Is DNA damaged ?

Question 11

Checkpoint failure causes?

Answer 11

Cell-cycle arrest and can lead to cell death by apoptosis

Question 12

Transit through the G1/S checkpoint requires an?

Answer 12

Active Cdk4/6-cyclinD complex

Question 13

Cdk4/6 is activated by?

Answer 13

Growth Factors

Question 14

P21 & p27 are?

Answer 14

Cdk inhibitors that inhibit that Cdk4/6

Question 15

p53 is a transcription factor induced by DNA damage that?

Answer 15

Controls expression of p21 and p27

Question 16

Mutation of DNA repair genes causes?

Answer 16

Genome Instability

Question 17

A single mutation is not enough. Each cancer arises from an accumulation of several mutations over a lifetime? Hypothesis

Answer 17

“Multi Hit”

Question 18

Genes mutated in cancer fall into which 2 groups?

Answer 18

Oncogenes and Tumor supressors

Question 19

What are Oncogenes?

Answer 19

Oncogenes are mutated forms of the normal genes that positively regulate cell division proto-oncogenes

Question 20

What are proto-oncogenes?

Answer 20

Normal genes that become cancer-causing genes if mutated and encode components of growth factor signalling pathways that stimulate cell proliferation by allowing progression from G0/G1 into S-phase when growth factors are present

Question 21

What is the main function of mutations?

Answer 21

They cause a gain of function in which the protein is increased in expression or activated in the absence of growth factors

Question 22

What are Tumor suppressor genes?

Answer 22

Tumour suppressor genes negatively regulate cell division, preventing abnormal proliferation, suppressing tumorigenesis

Question 23

How do tumor suppressor genes control cell division?

Answer 23

Encode proteins at cell cycle checkpoints through G1/S and G2/M if there is a problem

Question 24

Mutations cause a loss of what?

Answer 24

Function

Question 25

In 30% of all cancers, activating mutations are found in the?

Answer 25

Ras protein

Question 26

In cells with activated Ras the pathway is always active and cell division is independent of growth factors which is an example of?

Answer 26

An oncogene

Question 27

What is the p53?

Answer 27

a Sensor for DNA damage

Question 28

What is the role of p53?

Answer 28

Causes cell-cycle arrest if DNA is damaged by upregulating expression of p21 and p27 that inhibit Cdk4/6 and the G 1 /S transition

Question 30

50% of all human cancers have inactivating mutations in?

Answer 30

p53, mainly in DNA binding domain

Question 31

Mutation of genes involved in DNA repair is common and gives rise to?

Answer 31

Genome instability which make further mutations likely