Tumor Suppressors

Question 1

what are tumor suppressors?

Answer 1

they are cutting the brakes, they are recessive, so it usually takes two hits to see the effect (recessive phenotype)

both copies must be mutated to see an affect

Question 2

Tumor suppressors are recessive so how are they developed?

Answer 2

many inherited conditions have one copy mutated; the other copy must be lost for cancer to develop

Question 3

What are the three classes of tumor suppressors?

Answer 3

RB: master break
CDK inhibitors
P53:

Question 4

What is retinoblastoma and what are the stats on it?

Answer 4

it is cancer of the retina

diagnosed between 1-3 years of age

40% of all cases are due to inheritance of tumor suppressor mutation in Rb

60% are sporadic cases, you are not inheriting it in Rb gene but when you are born it occurs

Question 5

What is the knudson two step model? hereditary vs sporadic

Answer 5

Hereditary: born with one bad RB gene (first hit) and the other one mutated after birth (second hit), early onset of the cancer, after earlier in life and it affects both eyes, it also affects other cancer in other tissues

Sporadic: you inherit two good RB genes and both hits occur after birth, this is later onset and it only affects one eye, and it has no other cancers associated with it

Question 6

What happens when retinoblastoma protein controls cell divison, the growth signals dominate (e.g. p53 or CDK inhibitors)

Answer 6

1. Cyclin-CDK complex is not activated
2. No P is added to RB
3. RB hangs onto E2F (and thus it prevents E2F from doing gene transcription)
4. Cell cycle halts

Question 7

What happens when retinoblastoma protein controls cell divison, loss of RB (or CDK inhibitors)

Answer 7

E2F free to make cell cycle proteins. cell division uncontrolled

Question 8

How does retinoblastoma protein controls cell divison?

Answer 8

1. Signal pathway caused production and activation of two types of proteins: Cyclins and cyclin-dependent kinases (CDKs). CDK phosphorylate Rb
2. Cyclin-CDK complex add P to Rb.
3. E2F is released resulting in production of proteins necessary for cell cycle to proceed (note: more detail on this step later in ppt)
4. P removed from Rb,E2F binds to Rb, and cell cycle stops until next appropriate time

Question 9

What are the Cyclin-CDK complex regulators?

Answer 9

G1: D4/6
G1/S: E2
S: A2
G2: A1
M: B1

Question 10

how is CDK activated?

Answer 10

3 step process
1. Wee1 kinase (dual kinase) - inhibitory phosphate –> inhibit cell cycle progression
2. CDC25 - removes inhibitory phosphates (removed but not activated)
3. CAK (cyclin activating kinase): activates CDK by phosphorylation –> cell cycle progression

Question 11

what is the cell cycle steps? (draw it out)

Answer 11

draw it

Question 12

what is the treatment of triple negative cells? draw it out

Answer 12

draw it out

Question 13

what does turning myc off do?

Answer 13

cells will either differneiate or die

Question 14

what does APC activation do?

Answer 14

occurs with proper chromatid alignment

Question 15

What happens during mitotic/spindle phase? active vs inactive

Answer 15

inactive APC: it causes separase and securin to stay attached and thus cohesin cannot break the sister chromatids
active APC: APC activates securin and separase cleaves off of it causing cohesion to break the sister chromatids