Tumour Pathology 4 Flashcards

1
Q

What is the cell cycle defined as?

A

The interval between mitotic divisions

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2
Q

What are the external factors that affect cell cycle control?

A

Hormones, growth factors, cytokines, stroma

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3
Q

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

A

Prior to restriction point - external stimuli

After restriction point - autonomous

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4
Q

Where do checkpoints in the cell cycle exist?

A

G1, G2 and metaphase

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5
Q

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

A

G1, G2

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6
Q

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

A

G1

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7
Q

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

A

G1

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8
Q

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

A

S phase

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9
Q

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

A

G1 or G2

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10
Q

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

A

M phase

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11
Q

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

A

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

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12
Q

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

A

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

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13
Q

What is the name given to the active enzyme complex?

A

CDK/cyclin complex

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14
Q

What is the effect of CDK/cyclin complexes?

A

Phosphorylate target proteins

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15
Q

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

A

Results in activation or inactivation of that substrate

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16
Q

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

A

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

17
Q

How are CDK’s and cyclins regulated?

A

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

18
Q

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

A

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

19
Q

What is the function of the pRb phosphoprotein?

A

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

20
Q

What are the environmental factors that can cause genetic damage?

A

Chemicals
Radiation
Oncogenic viruses

21
Q

How do chemicals cause carcinogenesis?

A

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
Q

What are the targets for radiation carcinogenesis?

A

Purine and pyrimidine bases

23
Q

Which forms of high energy radiation are carcinogenic?

A

Ultraviolet radiation
X rays
Gamma radiation

24
Q

Which genes mutate at G1-S to cause cancer?

A

Rb, CDK4, Cyclin D and p16

25
Q

What is the function of P53?

A

Maintains genomic integrity

26
Q

When do levels of p53 increase?

A

When the cell is damaged

27
Q

What is the effect of increased levels of P53?

A

Cell cycle arrest at G1
Facilitates DNA repair
Apoptosis

28
Q

What is the effect of a mutated P53 gene?

A

No G1 arrest or repair of DNA

•Genetically damaged cells proliferate and form malignant neoplasms