Tumour Pathology 4 Flashcards

1
Q

How does cell division occur?

A

Normal cell cycle and mitosis

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2
Q

What do checkpoints do?

A
  • monitor and regulate process

- prevent progression at specific points

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3
Q

Examples of checkpoint and their function?

A

the G1 checkpoint at the G1/S transition

-Once the cell passes the G1 checkpoint and enters S phase, it becomes irreversibly committed to division.

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4
Q

What is the cell cycle?

A

The ordered sequence of events that occur in a cell in prep for cell division.
four-stage process in which the cell increases in size (G1), copies its DNA (S), prepares to divide/mitosis (G2, ), and divides (mitosis, or M, stage).

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5
Q

What external factors are involved in cell cycle control?

A
  • hormones
  • growth factors
  • cytokines
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6
Q

What phases of the cell cycle are referred to as Interphase?

A

G1
S
G2

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7
Q

Describe some cell cycle checkpoints

A

If cell size is inadequate, it stops at G1 or G2

  • if nutrient supply is inadequate it stops at G1
  • DNA is not replicated, it stops at S
  • Chromosome mis-alignment, M arrest
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8
Q

What are the checkpoint activators?

A
  • Enzymes

- A catalytic sub-unit activated by a regulatory sub-unit cyclin

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9
Q

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

A

Cyclin-dependent kinases (CDKs)

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10
Q

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

A

Cyclins

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11
Q

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

A

A CDK/cyclin complex

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12
Q

How do CDK/Cyclin complexes regulate the cell cycle?

A

Active CDK/cyclin complex phosphorylates target proteins

  • > results in activation/inactivation of target proteins
  • > substrate regulate events in the next cell cycle phase
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13
Q

What two things regulates CDK activity?

A
  • Cyclin production/destruction

- CDK inhibitors (CKIs)

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14
Q

What does the retinoblastoma gene code for?

A

A protein called pRb

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15
Q

What does pRb do?

A

When pRb is phosphorylated it becomes inactive and loses affinity/activates for E2F transcription factor
(applies a brake to the cell cycle)

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16
Q

How is E2F normally activated?

A

By Cyclin D/CDK complex phosphorylating (inactivating) pRb

17
Q

What are the 3 types of enviromental carcinogens?

A
  • Chemicals (e.g. aflatoxin)
  • Radiation
  • Oncogenic Viruses (E.g. Herpes, HEp B
18
Q

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

A

A DNA adduct

19
Q

What are the purines?

A

Adenine & guanine

20
Q

What are the Pyrimidines?

A

Cytosine & Thymine

21
Q

Where does radiation damage DNA?

A

Targets Purine & pyrimidine bases

22
Q

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

A
  • Cyclin D-pRb-E2F pathway

- p53 pathway

23
Q

How does a mutated retinoblastoma gene cause cancer?

A

Mutated REtinoblastoma gene

  • > Absetn or inactive pRb
  • > Overactive E2F transcription factor
  • > drives cell proliferation
24
Q

Dysregulation at which checkpoint causes most Cancers?

A

The G1-S checkpoint

25
Q

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

A

Rb (retinoblastoma)
CDK4
Cyclin D
p16

26
Q

What is teh general purpose of p53?

A
  • To maintain genomic integrity

- Binds to DNA in response to DNA damage

27
Q

How does p53 maintain the genomes integrity?

A

Activation of p53 leads to

  • cell cycle arrest at G1 to facilitate DNA repair.
  • transcriptional up-regulation of the CDK inhibitor p21 and the GADD45 (growth arrest and DNA damaged genes)
28
Q

What happens if p53 is mutated?

A
  • Theres no G1 arrest or DNA repair

- So genetically damaged cells proliferate & form malignant neoplasmT

29
Q

What is carcinogenesis?

A
  • failure of cell cycle control

- balance between proliferation and apoptosis is disrupted