Neoplasia (7) - Insensitivity to Growth Inhibition

Question 1

What are the 3 tumor suppressor genes?

Answer 1

RB
TP53
APC

Question 2

Normal job of tumor suppressor genes?

Answer 2

STOP signaling that causes aberrant cell growth

Question 3

Retinoblastoma gene

Answer 3

RB

Question 4

What is Knudson’s Hypothesis?

Answer 4

1. Germline mutations only require 1 more mutation

2. Somatic mutations require 2 mutations

Question 5

Active RB is ____phosphorylated

Answer 5

HYPOphosphorylated

Question 6

Inactive RB is ____phosphorylated

Answer 6

HYPERphosphorylated

Question 7

If RB is active, what does it bind to?

Answer 7

E2F transcription factor

Question 8

If RB is active, what is the end result?

Answer 8

• Binds to E2F transcription factor
• BLOCKS transcription from occurring
  = Cell will NOT go from G1 to S phase of cell cycle for cell division and proliferation

Question 9

If RB is inactive, what is the end result?

Answer 9

• Cannot bind to E2F transcription factor
• E2F transcribes the DNA for cell cycle progression
  = Cell WILL transition from G1 to S phase for Cell division and proliferation!!

Question 10

RB is inactive or active for cancer to result?

Answer 10

Inactive (hyperphosphorylated)

Question 11

Activation of ____ will cause an active RB (hypophosphorylated)

Answer 11

P16

- BLOCKS cyclins

Question 12

Activation of ____ will cause an inactive RB (hyperphosphorylated)

Answer 12

Cyclin D

- Phosphorylates it!

Question 13

Describe how Cyclin D causes the progression of the cell cycle and thus cell proliferation/growth/cancer?

Answer 13

Cyclin D will phosphorylate RB
RB will be inactive
RB will NOT bind to E2F
E2F will transcribe cell progression DNA
Cell will transition from G1 to S phase and divide

Question 14

What normally causes P53 to become active?

Answer 14

DNA damage

Question 15

What 3 ways does P53 prevent DNA damage from accumulating?

Answer 15

Activates repair
Activates cell senescence (permanent cell cycle arrest)
Activates Pro-Apoptosis molecules (BAX)

Question 16

If P53 is not active, what will result?

Answer 16

Damaged DNA will not be fixed and the cell will continue to divide and proliferate with mutations that will cause cancer

Question 17

What syndrome is an inherited Germline mutation of TP53?

Answer 17

Li-Fraumeni Syndrome

Question 18

Li-Fraumeni Syndrome

Answer 18

Germline mutation of TP53

Question 19

What symptoms will those with Li-Fraumeni Syndrome have?

Answer 19

YOUNG AGE when cancers arise
Diverse tumors
Family history

Question 20

APC

Answer 20

Adenomatous Polyposis Coli

Question 21

What receptor is on the cells that use APC?

Answer 21

WNT

Question 22

Normally, NO stimulation of the WNT receptor will cause?

Answer 22

APC binds and degrades Beta-Cantenin so no transcription of cell cycle progression will occur

Question 23

Normally, stimulation of the WNT receptor will cause?

Answer 23

APC dissociates from Beta-Cantenin and transcription of cell cycle progression WILL occur

Question 24

If APC is mutated, what results?

Answer 24

APC will NEVER bind Beta-Cantenin to degrade it and stop cell cycle transcription and progression so the cell will always be dividing and proliferating

Question 25

When APC is active, what does it normally do?

Answer 25

Bind and degrade Beta-Cantenin so cell cycle progression can NOT occur

Question 26

Familial Adenomatous Polyposis Coli (FAP)

Answer 26

Germline mutation of APC

Question 27

What are the symptoms seen with Familial Adenomatous Polyposis Coli (FAP)?

Answer 27

Colon polyps develop EARLY IN LIFE

- Germline mutation of APC