Tumour Pathology 4

Question 1

What is the cell cycle defined as?

Answer 1

The interval between mitotic divisions

Question 2

What are the external factors that affect cell cycle control?

Answer 2

Hormones, growth factors, cytokines, stroma

Question 3

When is the cell cycle dependant on external stimuli and when is it autonomous?

Answer 3

Prior to restriction point - external stimuli

After restriction point - autonomous

Question 4

Where do checkpoints in the cell cycle exist?

Answer 4

G1, G2 and metaphase

Question 5

If the cell size is inadequate, which checkpoint will cease the cell cycle?

Answer 5

G1, G2

Question 6

If the nutrient supply is inadequate, which checkpoint will cease the cell cycle?

Answer 6

G1

Question 7

If there is a lack of external stimulus, which checkpoint will cease the cell cycle?

Answer 7

G1

Question 8

If the DNA is not replicated, where will the cell cycle cease?

Answer 8

S phase

Question 9

If DNA damage is detected, where will the cell cycle cease?

Answer 9

G1 or G2

Question 10

If there is chromosome misalignment, where will the cell cycle cease?

Answer 10

M phase

Question 11

What is the main purpose of the G1, G2 and M phase checkpoints?

Answer 11

G1 - Checks DNA integrity
G2 - Checks proper chromosome duplication
M - Assesses attachment of each kinetochore to a spindle fiber

Question 12

What are the catalytic sub-units called and what are they activated by?

Answer 12

Cyclin dependant kinases Activated by a regulatory sub-units called cyclins

Question 13

What is the name given to the active enzyme complex?

Answer 13

CDK/cyclin complex

Question 14

What is the effect of CDK/cyclin complexes?

Answer 14

Phosphorylate target proteins

Question 15

What is the result of the CDK/cyclin complexes phosphorylating the target proteins?

Answer 15

Results in activation or inactivation of that substrate

Question 16

What is the function of the substrates that are inactivated or activated by CDK/cyclin complexes?

Answer 16

Substrates regulate what happens in the next phase of the cell cycle

Question 17

How are CDK’s and cyclins regulated?

Answer 17

CDK’s are constitutively expressed in an inactive form
Cyclins accumulate and are destroyed as cycle progresses
CDK inhibitors

Question 18

What are the two methods of inhibition of the CDK inhibitors?

Answer 18

Bind to CDK and prevent the association of these CDK’s with their cyclin regulatory proteins. They bind to the CDK/cyclin complexes

Question 19

What is the function of the pRb phosphoprotein?

Answer 19

CDK/cyclin complexes phosphorylate this protein. Once phosphorylated it becomes inactive and loses affinity for the E2F transcription factor.This free E2f now activates vital target genesE2F is a potent stimulator of cell cycle entry

Question 20

What are the environmental factors that can cause genetic damage?

Answer 20

Chemicals
Radiation
Oncogenic viruses

Question 21

How do chemicals cause carcinogenesis?

Answer 21

Oxidising and alkylating agents damage bases.Carcinogens or their metabolites react with DNA forming DNA adducts. The formation of these covalently bound products at particular chromosome sites causes cancer.

Question 22

What are the targets for radiation carcinogenesis?

Answer 22

Purine and pyrimidine bases

Question 23

Which forms of high energy radiation are carcinogenic?

Answer 23

Ultraviolet radiation
X rays
Gamma radiation

Question 24

Which genes mutate at G1-S to cause cancer?

Answer 24

Rb, CDK4, Cyclin D and p16

Question 25

What is the function of P53?

Answer 25

Maintains genomic integrity

Question 26

When do levels of p53 increase?

Answer 26

When the cell is damaged

Question 27

What is the effect of increased levels of P53?

Answer 27

Cell cycle arrest at G1
Facilitates DNA repair
Apoptosis

Question 28

What is the effect of a mutated P53 gene?

Answer 28

No G1 arrest or repair of DNA

•Genetically damaged cells proliferate and form malignant neoplasms