ANALYSIS OF 2 INBRED STRAINS OF MICE DERIVED FROM THE SENCAR STOCK WITH DIFFERENT SUSCEPTIBILITY TO SKIN TUMOR PROGRESSION

The SENCAR stock of mice has proved to be a useful model in dissecting out the multistage nature as well as the critical mechanisms involved in skin tumorigenesis. This outbred stock was selectively bred to be susceptible to initiation with 7,12-dimethylbenz[a]anthracene (DMBA) a nd promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA), In order to obtain mice more suitable for genetic analyses of tumor susceptibi lity and tissue transplantation studies, several inbred lines of mice were derived from the SENCAR stock, One of these lines, the SSIN mice, has a higher susceptibility to tumor promotion compared to the SENCAR stock but is very resistant to tumor progression, On the other hand, the SENCAR B/Pt mice, derived also from the outbred stock, not only ha ve a tumor promotion susceptibility almost identical to the SSIN mice, but they also have a high susceptibility to tumor progression, In ord er to understand the nature of the phenotypic differences between thes e two inbred lines me have characterized them using several parameters and markers that are associated with the progression of papillomas to squamous cell carcinoma (SCC), In this sense we analysed the tumor mu ltiplicity and SCC incidence, and the expression of markers of progres sion and cell cycle related proteins in papillomas derived front both strains, Our results showed that while both strains have a similar pap illoma multiplicity and incidence the SENCAR B/Pt mice have 67% incide nce of SCC, compared to 0% in the SSIN, SENCAR B/Pt papillomas at 30 w eeks of promotion have a higher and aberrant expression of K13, and lo ss of connexin 26, TGF-beta 1 was found to be over-expressed in the su prabasal and superficial cells in the SENCAR B/Pt papillomas, while it was only expressed in the superficial cell layer in those derived fro m SSIN, The SENCAR B/Pt papillomas also showed an enlarged proliferati ve compartment with overexpression of cyclin D1 and PCNA as seen by im munohistochemistry and Western blot.