Tumour Pathology 4 Flashcards Preview

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Flashcards in Tumour Pathology 4 Deck (28):
1

What is the cell cycle defined as?

The interval between mitotic divisions

2

What are the external factors that affect cell cycle control?

Hormones, growth factors, cytokines, stroma

3

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

Prior to restriction point - external stimuli After restriction point - autonomous

4

Where do checkpoints in the cell cycle exist?

G1, G2 and metaphase

5

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

G1, G2

6

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

G1

7

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

G1

8

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

S phase

9

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

G1 or G2

10

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

M phase

11

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

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

12

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

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

13

What is the name given to the active enzyme complex?

CDK/cyclin complex

14

What is the effect of CDK/cyclin complexes?

Phosphorylate target proteins

15

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

Results in activation or inactivation of that substrate

16

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

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

17

How are CDK's and cyclins regulated?

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

18

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

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

19

What is the function of the pRb phosphoprotein?

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 genes E2F is a potent stimulator of cell cycle entry

20

What are the environmental factors that can cause genetic damage?

Chemicals Radiation Oncogenic viruses

21

How do chemicals cause carcinogenesis?

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.

22

What are the targets for radiation carcinogenesis?

Purine and pyrimidine bases

23

Which forms of high energy radiation are carcinogenic?

Ultraviolet radiation X rays Gamma radiation

24

Which genes mutate at G1-S to cause cancer?

Rb, CDK4, Cyclin D and p16

25

What is the function of P53?

Maintains genomic integrits

26

When do levels of p53 increase?

When the cell is damaged

27

What is the effect of increased levels of P53?

Cell cycle arrest at G1 Facilitates DNA repair Apoptosis

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28

What is the effect of a mutated P53 gene?

No G1 arrest or repair of DNA

 

•Genetically damaged cells proliferate and form malignant neoplasms