Tumour Pathology 4 Flashcards

1
Q

What is the cell cycle?

A

The time between mitotic divisions

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2
Q

4 phases of the cell cycle?

A
  • Mitosis (M)
  • Synthesis of DNA synthesis components (G1)
  • DNA synthesis (S)
  • Prep for mitosis (G2)
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3
Q

What external factors are involved in cell cycle control?

A
  • Hormones
  • Growth Factors
  • Cytokines
  • stroma
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4
Q

What intrinsic factors help control the cell cycle?

A

Critical checkpoints such as teh restriction point (R) just before G1.
Crossing these checkpoints requires external stimuli to continue.

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5
Q

What phases of teh cell cycle are referred to as interphase?

A

G1
S
G2

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6
Q

Describe some cell cycle checkpoints:

A
  • IF teh cell size is inadequate it stops at G1 or G2
  • If nutrient supply inadequate, stops at G1
  • DNA not replicated, stops at S
  • Chromosome mis-alignment, M arrest
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7
Q

What makes up the checkpoints?

A

Enzymes.

Specifically a catalytic sub-unit activated by a regulatory sub-unit

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8
Q

What are the catalytic sub-units in cell cycle checkpoints?

A

Cyclin-dependent kinases (CDKs)

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9
Q

What are the regulatory sub-units in cell cycle checkpoints called?

A

Cyclins

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10
Q

What do call teh active enzyme complex in a cell cycle checkpoint?

A

A CDK/cyclin complex

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11
Q

How do CDK/Cyclin complexes regulate the cell cycle?

A

CDK/cyclin complex phosphorylates a substrate

  • > substrate is either activated or inactivated
  • > substrate regulates the next cell cycle
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12
Q

What two things regulates CDK activity?

A
  • Cyclin production/destruction

- CDK inhibitors (CKIs)

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13
Q

What does the retinoblastoma gene code for?

A

A protein called pRb

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14
Q

What does pRb do?

A

When activated it Inactivates E2F transcription factor

applies a brake to the cell cycle

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15
Q

How is E2F normally activated?

A

By Cyclin D/CDK complex phosphorylating (inactivating) pRb

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16
Q

What are the 3 types of enviromental carcinogens?

A

Chemicals (e.g. aflatoxin)
Radiation
Oncogenic Viruses (E.g. Herpes, HEp B)

17
Q

What do you call a section of DNA attached to a chemical carcinogen?

A

A DNA adduct

18
Q

What are the purines?

A

Adenine & guanine

19
Q

What are the Pyrimidines?

A

Cytosine & Thymine

20
Q

Where does radiation damage DNA?

A

Targets Purine & pyrimidine bases

21
Q

Name 2 cell cycle regulatory pathways frequently disrupted to cause cancer?

A
  • Cyclin D-pRb-E2F pathway

- p53 pathway

22
Q

How does a mutated retinoblastoma gene cause cancer?

A

Mutated REtinoblastoma gene

  • > Absetn or inactive pRb
  • > Overactive E2F transcription factor
  • > drives cell proliferation
23
Q

Dysregulation at which checkpoint causes most Cancers?

A

The G1-S checkpoint

24
Q

What genes are commonly mutated to cause G1-S dysregulation?

A

Rb (retinoblastoma)
CDK4
Cyclin D
p16

25
Q

What is teh general purpose of p53?

A

To maintain genomic integrity

26
Q

How does p53 maintain the genomes integrity?

A

p53 builds up in damaged cells:

  • cell cycle arrest at G1 to facilitate DNA repair
  • in severe cases p53-induced apoptosis
27
Q

What happens if p53 is mutated?

A

Theres no G1 arrest or DNA reapir so:

genetically damaged cells proliferate & form malignant neoplasms