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Flashcards in tumour pathology 4 Deck (27)
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1

what is a cell cycle?

the interval between mitotic divisions

2

what are the phases of the cell cycle, and what happens in each?

1. G1 - synthesis of components required for DNA synthesis
2. S - DNA synthesis
3. G2 -preparation for mitosis
4. M - mitosis and cell division

G0- extension of G1, quiescent state, dormant

3

when does DNA repair occur?

G2 phase

4

when can the cell cycle be affected by external factors?

in the G1 phase

5

examples of external factors

hormones, cytokines, growth factors, stroma

6

where are the checkpoints of the cell cycle?

-G1 checkpoint at the G1/S transition
-G2 checkpoint at -the G2/M transition
-M checkpoint between metaphase and anaphase

7

where is the cell cycle arrested if cell size is inadequate?

G1 or G2

8

where is the cell cycle arrested if nutrient supply is inadequate?

G1

9

where is the cell cycle arrested if essential external stimuli are lacking?

G1

10

where is the cell cycle arrested if DNA is not replicated?

S

11

where is the cell cycle arrested if DNA is damaged?

G1 or G2

12

where is the cell cycle arrested if chromosomes mis-align

M-phase

13

how do checkpoints work?

1. cyclin dependent kinases are present in the cell
2. cyclin levels rise if the checkpoint has the go-ahead.
3. these bind to CDKs, activating them.
4. the active CDKs then act by phosphorylating sybstrates
5. these phosphorylated substrates are required for the next stage of the cell cycle

the cell cycle is also regulated using CDK inhibitors

14

what does INK4A inhibit?

CDK4

15

INK4A inhibitors

p16^INK4A
p15^INK4B
p18^INK4C
p19^INK4D

16

CIP/KIP inhibitors

p21^CIP1

17

what does the retinoblastoma gene encode for?

pRb

18

when is pRb active?

when it is hypophosphorylated

19

when is pRb inactive?

when it has been phosphorylated by cyclin D/CDK complexes

20

what is the function of pRb?

E2F transcription factor, this activates vital target genes for the stimulation of cell cycle entry

21

how do oxidising and alkylating agents cause carcinogenesis?

they critically damage purine and pyrimidine bases in DNA

22

what is a DNA adduct?

covalently bound products of DNA and a chemical carcinogen

23

how does radiation damage DNA?

damages the purine and pyrimidine bases

24

types of ionising radiation

-UV (UV-B in sunlight)
-X-rays
-Gamma radiation

25

what are the two regulatory pathways regularly disrupted to cause cancer?

1. The cyclin D-pRb-E2F pathway

2. p53 pathway

26

which checkpoint is usually dysregulated in cancer cells and which four genes are mutated?

G1/S checkpoint

Rb, CDK4, cyclin D and p16

27

p53 function

maintains genomic integrity.
does this by inducing cell cycle arrest at G1 or facilitating DNA repair or inducing apoptosis if DNA damage is severe