Carcinogenesis : molecular hallmarks of cancer cells

Question 1

What 2 events need to happen in order for neoplasia to occur?

Answer 1

1) Oncogene activation

2) Tumour Suppressor gene inactivation

Question 2

What are caretaker genes

Answer 2

are a type of tumour suppressor gene. they maintain genetic stability by repairing damaged DNA and replication errors

Question 3

What genes maintain genetic stability by repairing damaged DNA and replication errors

Answer 3

caretaker genes

Question 4

What happens when caretaker genes are inactivated?

Answer 4

a higher rate of mutations than normal&raquo_space;>greater risk of cancer

Question 5

What are gatekeeper genes?

Answer 5

Gatekeeper are a type of Tumour Suppressor genes play an important role in regulating normal growth.

• negative regulator of cell cycle and proliferation
• positive regulator of apoptosis.
• Positive regulators of cell differentiation.

Question 6

What is the effect of carcinogens on Tumour suppressor genes?

Answer 6

Loss of function of TSGs

Question 7

What is 2nd hit inactivation of TSG?

Answer 7

The 1st hit in TSG inactivation usually doesn’t have an effect because of the remaining normal copy.

2nd hit of the TSG results in complete loss of function,

Question 8

Name some TSGs and familial cancer syndromes

Answer 8

• retinoblastoma
• Li-Fraumeni
• Familial adenomatoud polyposis
• familial breast cancer
• Hereditary non polyposis colorectal cancer

Question 9

What genes promote cell proliferation, survival, angiogenesis and negative regulation of apoptosis?

Answer 9

Proto oncogenes

Question 10

What gene mutations leads to activated versions of protooncogenes and gain of function?

Answer 10

Oncogenes

Question 11

oncogenes

Answer 11

cause increased levels of cell proliferation, survival, angiogenesis and inhibition of apoptosis

Question 12

How many copies of the oncogene need to be activated in order to induce a gain of function?

Answer 12

1

the mutated gene is dominant to the other normal parental gene

Question 13

What are the mechanisms of oncogene activation?

Answer 13

-TRANSLOCATION
(of a proto-oncogene from a low transcriptionally active site to an active site leads to increased expression of the oncogene)

-POINT MUTATION
(substitution of a single base pair can alter an amino acid in the protein causing it to become hyperactive)

-AMPLIFICATION
(by insertion of multiple copies of the oncogene leads to increased expression.)

Question 14

Why are tumour cells said to be self sufficient in growth signals?

Answer 14

Normal cells require signalling by growth factors before they proliferate.

Tumours have the ability to grow in the absence of growth factors.

Question 15

What is the association between tumour cells and antigrowth signals/

Answer 15

In normal cells cell division will stop in response to negative growth factors and leave the cell cycle.

Tumour cells do not respond to these antigrowth signals so continue to proliferate.

Question 16

What is the significance of the RB gene in tumour cells?

Answer 16

The RB gene regulate the cell cycle.

In tumours the RB gene is inactivated so leads to resistance in negative growth factor regulation.

Question 17

What do tumour cells express that makes them immortal?

Answer 17

Telemorase replaces the lost material in DNA. This allows the cell to become immortal.

Question 18

What is the association between tumours and apoptosis?

Answer 18

normal cells apoptose in abnormal stress / growth.

tumour cells lose the ability to apoptose.

Question 19

What gene induces apoptosis?

Answer 19

TP53

TP53 induces cell cycle arrest to allow repair of DNA damage.

TP53 also induces apoptosis if too much damage.

in TP53 inactivation there is a loss of the apoptotic response.

Question 20

What happens when TP53 is inactivated

Answer 20

loss of apoptosis

Question 21

When is the TP53 mutation inherited?

Answer 21

Li-Fraumeni

Question 22

What mutation is inherited in Li-Fraumeni?

Answer 22

TP53 mutation is inherited in Li-Fraumeni

Question 23

What is the association between vascular endothelial growth factor and tumours?

Answer 23

Tumours need to stimulate a new blood supply (angiogenesis)

They secrete vascular endothelial growth factor that stimulated the growth of new vessels.

Question 24

What is the function of E-Cadherin and what is its association with tumours?

Answer 24

E-Cadherin is a adhesion molecue that helps epithelial cells to be held together.

Tumour cells lose E-Cadherin. The cells become motile&raquo_space;>metastasis.

Question 25

what is the association between HER2 and Herceptin?

Answer 25

HER2 codes for a +ve growth factor receptor.

Herceptin is a drug targeted at HER2 and dampens the effects of an overactive HER2.