Skin cancers 3 Flashcards
Stages of cSCC according to mouse model?
Normal skin–> hyperplastic epidermis–> papilloma–> SCC
What does the induction of skin carcinomas require?
Certain combinations of treatments w/ tumour initiators and tumour promoters
Result after 3 months if only the initiator is used?
No change
Result 3 months after multiple paintings w/ promoter?
No change
Result after painted once w/ initiator, followed by multiple paintings w/ promoter?
Papilloma
Result after painted once w/ initiator in one area, followed by multiple paintings w/ promoter in a diff area?
No change
Result if a papilloma is painted with the promoter?
Papilloma remains
Result if a papilloma is painted with an initiator?
Carcinoma forms
How was an advanced papilloma formed?
Painted with initiator, repeated promoter treatments followed by additional promoter treatments
What occurred when promoter treatment was halted on a papilloma?
The papilloma regressed
Result of promoter treatment on an uninitiated cell?
No effect
Result of halting promoter treatment on an advanced papilloma?
Promoter-independent papilloma is formed
What treatment can result in the formation of carcinoma from an advanced papilloma?
Additional promoter treatments
Second painting with initiator
What causes a reversible effect, the tumour initiator or the tumour promoter?
Promoter
What causes a irreversible effect, the tumour initiator or the tumour promoter?
Initiator
Why does the initiator cause an irreversible effect?
It causes a genetic alteration
Why does the promoter cause an reversible effect?
It exerts a nongenetic effect
What is the tumour initiator used?
DMBA
What exactly does DMBA cause?
Genetic mutations in the DNA of epidermal cells–> especially in stem cells
What is notable about the papillomas that emerge after DMBA treatment?
They have point mutations that lead to activation of the hRAS oncogene
Does the hRAS mutation alone (caused by DMBA) have an effect on the cell?
No
When does the hRAS mutation have an effect on the cell?
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
What occurs as a result of hRAS induced growth and division cycles?
Leads to clonal expansion and the formation of a papilloma
Result of halting the TPA treatment?
Papilloma regresses
Result of exposing a papilloma to a second dose of DMBA?
Mutation (inactivation) in p53 protein
Result of mutation (inactivation) in p53 protein?
The population of cells are no longer dependent on the tumour promoter, and are capable of forming cSCC w/o it
How does TPA act as a tumor promoting agent?
Via activation Protein kinase C alpha
Which signalling pathways does protein kinase c alpha activate?
MAPKinase, NF-kappaB, AP1 TF complexes
What is the result of activation of the three signalling pathways that protein kinase c alpha activates?
Transcription of genes that are important in cell proliferation
Why does repeated paintings of TPA lead to clonal expansion?
It ends up stimulating proliferative genes
