Skin cancers 3

Question 1

Stages of cSCC according to mouse model?

Answer 1

Normal skin–> hyperplastic epidermis–> papilloma–> SCC

Question 2

What does the induction of skin carcinomas require?

Answer 2

Certain combinations of treatments w/ tumour initiators and tumour promoters

Question 3

Result after 3 months if only the initiator is used?

Answer 3

No change

Question 4

Result 3 months after multiple paintings w/ promoter?

Answer 4

No change

Question 5

Result after painted once w/ initiator, followed by multiple paintings w/ promoter?

Answer 5

Papilloma

Question 6

Result after painted once w/ initiator in one area, followed by multiple paintings w/ promoter in a diff area?

Answer 6

No change

Question 7

Result if a papilloma is painted with the promoter?

Answer 7

Papilloma remains

Question 8

Result if a papilloma is painted with an initiator?

Answer 8

Carcinoma forms

Question 9

How was an advanced papilloma formed in the mouse model?

Answer 9

Painted with initiator, repeated promoter treatments followed by additional promoter treatments

Question 10

What occurred when promoter treatment was halted on a papilloma?

Answer 10

The papilloma regressed

Question 11

Result of promoter treatment on an uninitiated cell?

Answer 11

No effect

Question 12

Result of halting promoter treatment on an advanced papilloma?

Answer 12

Promoter-independent papilloma is formed

Question 13

What treatment can result in the formation of carcinoma from an advanced papilloma?

Answer 13

Additional promoter treatments
Second painting with initiator

Question 14

What causes a reversible effect, the tumour initiator or the tumour promoter?

Answer 14

Promoter

Question 15

What causes a irreversible effect, the tumour initiator or the tumour promoter?

Answer 15

Initiator

Question 16

Why does the initiator cause an irreversible effect?

Answer 16

It causes a genetic alteration

Question 17

Why does the promoter cause an reversible effect?

Answer 17

It exerts a nongenetic effect

Question 18

What is the tumour initiator used?

Answer 18

DMBA

Question 19

What does DMBA cause?

Answer 19

Genetic mutations in the DNA of epidermal cells–> especially in stem cells

Question 20

What is notable about the papillomas that emerge after DMBA treatment?

Answer 20

They have point mutations that lead to activation of the hRAS oncogene

Question 21

Does the hRAS mutation alone (caused by DMBA) have an effect on the cell?

Answer 21

No

Question 22

When does the hRAS mutation have an effect on the cell?

Answer 22

In the presence of repeated stimulation (paintings with TPA), the cell bearing the activated hRAS oncogene is induced to pass through repeated growth and division cycles

Question 23

What occurs as a result of hRAS induced growth and division cycles?

Answer 23

Leads to clonal expansion and the formation of a papilloma

Question 24

Result on papilloma of halting the TPA treatment?

Answer 24

Papilloma regresses

Question 25

Result of exposing a papilloma to a second dose of DMBA?

Answer 25

Mutation (inactivation) in p53 protein

Question 26

Result of mutation (inactivation) in p53 protein?

Answer 26

The population of cells are no longer dependent on the tumour promoter, and are capable of forming cSCC w/o it

Question 27

How does TPA act as a tumor promoting agent?

Answer 27

Via activation Protein kinase C alpha

Question 28

Which signalling pathways does protein kinase c alpha activate?

Answer 28

MAPKinase, NF-kappaB, AP1 TF complexes

Question 29

What is the result of activation of the three signalling pathways that protein kinase c alpha activates?

Answer 29

Transcription of genes that are important in cell proliferation

Question 30

Why does repeated paintings of TPA lead to clonal expansion?

Answer 30

It ends up stimulating proliferative genes