L30 Cancer Pathobiology 2

Question 1

How is Ras1 turned on and off?

Question 2

What is Ras 1?

Question 3

What are directly linked to switching on Ras?

Answer 3

Growth factors

Question 4

What is the importance of ras in growth factor-induced growth?

Answer 4

1. Cell growth
2. Gene expression
3. Cell morphology and movement.

Question 5

slide 30

Question 6

True or False:The concept of dominant oncogenes alone, cannot explain cancer cell behaviour

Answer 6

True

Question 7

How was this staement proved: “The concept of dominant oncogenes alone, cannot explain cancer cell behaviour”.

Answer 7

Cell fusion experiments forming a hypothesis that normal cells express tumour suppressor genes that are lost during oncogenesis.

Question 8

Might tumor suppresor genes exist?

Answer 8

Yes - loss of growth suppresor gene more likely than gain of function oncogene mutation.
No - loss of both alleles of putative growth suppressor genes unlikely.

Question 9

How is retinoblastoma developed?

Answer 9

They arise sporadically( ususally only affects one eye) as well as in familiies (Almost always affects both eyes).

Question 10

What did knudsen propose in context with his one/two hit hypothesis?

Question 11

Why is knudsens hypothesis important?

Answer 11

Provides evidence:
1. for tumour suppressor gene hypothesis
2. that cancer requires loss of both wild-type alleles
3. for the basis of inherited predisposition to cancer

Question 12

What evidence does cytogenetics provide in inherited retinoblastoma?

Answer 12

They provide evidence for a Chr13 deletion.

Question 13

Slide 38

Question 14

What are the difference between oncogenes and tumor suppressor genes?

Answer 14

1. Effect of mutation:
   Activating gain of function dominat in oncogenes and inactivating loss of function recessive in tumor suppresor.
2. No. of alleles mutated to exert effect:
   One in oncogenes and two in Tumour supp genes.
3. Effect on function of the protein product: Enhaamce in oncogenes and reduced in Tum supp genes.

Question 15

What is tumorogenesis?

Answer 15

Tumorigenesis is the process by which normal cells in the body are transformed into cancer cells.

Question 16

Can one mutation cause tumorigenesis?

Answer 16

More than one mutation is required for tumorigenesis

Question 17

What underpins tumour progression?

Answer 17

Successive rounds of random inherited change and natural selection underpins tumour progression

Question 18

Are cancer cells genetically stable?

Answer 18

No, cancer cells are genetically unstable and is one of the reasons tumor grown relatively slowly.

Question 19

What are the causes of genetic instability?

Answer 19

Defects in:
* DNA repair pathways
* Correction mechanisms for DNA replication errors.
* Correction mechanisms for DNA segregation errors>

Question 20

How is apoptosis induced in normal cells?

Answer 20

Through cellular stress such as DNA damage.

Question 21

What factors in context with apoptosis contribute to tumorigenesis?

Answer 21

Incraesed cell division and decreased apoptosis.

Question 22

How do normal cells respond to cellular stress?

Answer 22

Through one criticasl signalling pathway, as the stressors increase the likely outcome is apoptosis.

Question 23

How is intrinsic apoptosis interupted?

Answer 23

Mutations in p53 and associated pathways disrupt intrinsic apoptosis.

Question 24

Give an example of a cell cycle checkpoint gene?

Answer 24

p53 is one example of a cell cycle checkpoint gene

Question 25

In which phase of the cell cycle does the checkpoint genes operate?

Answer 25

Several checkpoint genes operate in the G1 phase.

Question 26

How does checkpoints contribute to genetic instability?

Answer 26

Loss of checkpoints contribute to genetic instability.