Proto-oncogens and Tumour suppressors

Question 1

Tumour suppressors

Answer 1

inhibit cell cycle progression and often cause cell death or DNA repair

Question 2

How can tumour suppressors cause cancer

Answer 2

when they become mutated

Question 3

the 2 hit hypothesis and tumour suppressors

Answer 3

for loss of function both suppressor genes must be mutated

Question 4

key tumour suppressors (6)

Answer 4

1) p53
2) APC
3) DCC
4) BRCA 1/2
5) Pten
6) Rb

Question 5

p53 is involved with

Answer 5

the majority of cancers

Question 6

Rb is involved with

Answer 6

retinoblastomas and osteogenic sarcomas

Question 7

APC is involved with

Answer 7

colon

Question 8

DCC is involved with

Answer 8

colon rectal

Question 9

BRCA 1/2 is involved with

Answer 9

breast cancer and ovarian cancer

Question 10

PTen is involved with

Answer 10

Gliomas , breast, thyroid

Question 11

how does p53 act as a tumour suppressor

Answer 11

1) damaged DNA activates ATM
2) ATM activates Chk1/2 which phosphorylates p53
3) causes Mdm2 to unbind p53
4) p53 goes to nucleus and transcribes apoptotic proteins as well as P21 and p27

Question 12

P21 and P27

Answer 12

cause cell cycle arrest –> DNA repair

Question 13

How does Rb act as a tumour suppressor ?

Answer 13

when Rb is bound to E2F it prevents it from translocation tot the nucleus
- therefore cyclin E and CDK2 are not transcribed

Question 14

when the Rb gene is mutated

Answer 14

oncogene- since it no longer prevents E2F from translocating to the nucleus

Question 15

APC stands for

Answer 15

adenomatous polyposis coli

Question 16

APC is part of

Answer 16

the B-catenin destruction complex

-acts by negatively regulating B-catenin 9 a cell growth factor)

Question 17

when Wnt isn’t bound

Answer 17

APC causes the ubiquitination and phosphorylation of B-catenin meaning it is sent to the proteasome and cannot transcribed cell growth genes

Question 18

Pten

Answer 18

Inhibits PIP3/Akt

-these usually promote cell proliferation and survival

Question 19

BRCA -1/2

Answer 19

Act as tumour suppressors by repairing DNA and causing cell death

Question 20

DCC is a tumour suppressor when

Answer 20

Netrin-1 isn’t bound- causes apoptosis by activating caspases

Question 21

Proto-oncogenes

Answer 21

encode different proteins which stimulate cell division, cell survival and inhibit differentiation

Question 22

porto-oncogenes mutate and become

Answer 22

oncogenes

Question 23

basic detail of how proto oncogenes can cause cancer

Answer 23

1) oncogene have a gain of function
2) uncontrolled cell division
3) tumour
4) cancer

Question 24

4 ways in which proto-oncogenes can mutate to oncogenes

Answer 24

1) deletion/ point mutation
2) regulatory mutation
3) gene amplification
4) chromosomal translocation

Question 25

deletion and point mutations

Answer 25

hyperactive proteins made in normal amounts

Question 26

2) regulatory mutation
3) gene amplification
4) chromosomal translocation

Answer 26

normal protein but greatly over expressed

Question 27

chromosomal translocation

Answer 27

hyperactive fusion protein

Question 28

oncogenes being therapeutic targets

Answer 28

targeting oncogenes with drugs which can inhibit their action will half uncontrollable cell growth, preventing tumour development

Question 29

Examples of proto-oncogenes

Answer 29

SMO, ``egfr,` raf, DCC, RAS

Question 30

SMO

Answer 30

smoothened; a proto-oncogene involved in Hh singalong that controls skin growth

Question 31

normal SMO

Answer 31

Hh binds to PTCH, allowing SMO to move to the cilium and activate GLI
- cell growth and development

Question 32

a mutated SMO

Answer 32

will have its signal on the whole time, causing constant activation of GLI- constant cell growth and development- uncontrollable forth and division

Question 33

EGFR (MAPK receptor)

Answer 33

• when over expressed: colorectal, pancreatic and lung cancer
• mutated: non-small cell lung cancer , glioblastoma

Question 34

RAF

Answer 34

• melanoma
• papillary thyroid cancer
• colon cancer

Question 35

DCC as a proto-oncogene

Answer 35

if this receptor is mutated to be turned not he whole time without entrain, it become a proto-oncogene

Question 36

RAS

Answer 36

• part of MAPK cascade
• provides signal which leads to cell division

if RAS mutates –> GTP is constantly bound leading to ERK being constantly activated

Question 37

RAS and which cancer

Answer 37

-pancreatic, colon, papillary thyroid cancer, non small cell lung cancer