Tumour Pathology 4

Question 1

System of cyclically active and inactive enzymes

Answer 1

Checkpoints

Question 2

catalytic subunits (checkpoints)

Answer 2

cyclin-dependent kinases (CDKs)

Question 3

regulatory sub-units (checkpoints)

Answer 3

cyclins

Question 4

What binds to CDK4 and 6 to prevent association CDKs with their cyclin regulatory proteins?

Answer 4

INK4A family

p16INK4A, p15INK4B, p18INK4C, p19INK4D

Question 5

2 main families of CDK inhibitors (CKIs)

Answer 5

INK4A family and CIP/KIP family

Question 6

What encodes phosphoprotein (pRb) ?

Answer 6

Retinoblastoma gene

Question 7

Important target of pRb

Answer 7

E2F transcription factor

Question 8

How do chemical carcinogen cause cancer?

Answer 8

DNA adduct (covalent bound DNA)

Question 9

Primary defect in cancer

Answer 9

Uncontrolled cell proliferation via cell cycle dysregulation

Question 10

Mechanism of cellular replication
Nuclear division plus cytokinesis
Generates two genetically identical daughter cells

Cell cycle - ordered series of events between mitotic divisions
Cell cycle must be in correct seq
DNA syn and mitosis

QC - checkpoints

Answer 10

How does cell division occur? Normal cell cycle and mitosis

Question 11

Interphase

Answer 11

Gap 1, Synthesis ( DNA syn). Gap 2 (Prep for mitosis)

Question 12

Quiescent phase

Answer 12

G0

Neurones and brains are in a permanent G0 phase
Hepatocytes - do have long G0 phase but not permanent

Question 13

Rate limiting step
Prevent progression at specific points monitor and regulate progress
Check for damaged DNA

Answer 13

G1/S restriction point

Question 14

Unreplicated or damaged DNA

Answer 14

S restriction point

Question 15

Cells with p53 defect do not undergo cell cycle arrest - accumulate - mutation/malignant tumour

Answer 15

P53

Question 16

Two regulatory pathways frequently disrupted -

Answer 16

The cyclin D-pRb-E2F pathway

p53 pathway

Question 17

Virtually all cancers are dysregulated at ….. because of mutation in one of four genes:

Answer 17

G1-S

Rb, CDK4, cyclin D and p16

Question 18

Absent or inactive …. releases the cell cycle brake

Answer 18

pRb

Rem by R (release cell cycle) b (brake)

Question 19

…… Maintains genomic integrity
Levels ….. in damaged cells
Induces cell cycle arrest at ……

Answer 19

p53
increase
G1

Facilitates DNA repair; If severe damage: p53-induced apoptosis (programmed cell death)

Cells with mutated p53 do not G1 arrest or repair damaged DNA; Genetically damaged cells proliferate and form malignant neoplasms