Analysis of two 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 outthe multistage nature as well as the critical mechanisms involved in skintumorigenesis. This outbred stock was selectively bred to be susceptible toinitiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion with12-O-tetradecanoylphorbol-13-acetate (TPA). In order to obtain mice moresuitable for genetic analyses of tumor susceptibility and tissuetransplantation studies, several inbred lines of mice were derived from theSENCAR stock. One of these lines, the SSIN mice, has a highersusceptibility to tumor promotion compared to the SENCAR stock but is veryresistant to tumor progression. On the other hand, the SENCAR B/Pt mice,derived also from the outbred stock, not only have a tumor promotionsusceptibility almost identical to the SSIN mice, but they also have a highsusceptibility to tumor progression. In order to understand the nature ofthe phenotypic differences between these two inbred lines we havecharacterized them using several parameters and markers that are associatedwith the progression of papillomas to squamous cell carcinoma (SCC). Inthis sense we analysed the tumor multiplicity and SCC incidence, and theexpression of markers of progression and cell cycle related proteins inpapillomas derived from both strains. Our results showed that while bothstrains have a similar papilloma multiplicity and incidence the SENCAR B/Ptmice have 67% incidence of SCC, compared to 0% in the SSIN. SENCAR B/Ptpapillomas at 30 weeks of promotion have a higher and aberrant expressionof K13, and loss of connexin 26. TGF-beta1 was found to be over-expressedin the suprabasal and superficial cells in the SENCAR B/Pt papillomas,while it was only expressed in the superficial cell layer in those derivedfrom SSIN. The SENCAR B/Pt papillomas also showed an enlarged proliferativecompartment with overexpression of cyclin D1 and PCNA as seen byimmunohistochemistry and Western blot.