Carcinogenesis, Vol 19, 125-132, Copyright © 1998 by Oxford University Press
MC Stern, IB Gimenez-Conti, I Budunova, L Coghlan, SM Fischer, J DiGiovanni, TJ Slaga and CJ Conti
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) and promotion with
12-O-tetradecanoylphorbol-13-acetate (TPA). In order to obtain mice more
suitable for genetic analyses of tumor susceptibility 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 have a tumor promotion
susceptibility almost identical to the SSIN mice, but they also have a high
susceptibility to tumor progression. In order to understand the nature of
the phenotypic differences between these two inbred lines we 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 multiplicity and SCC incidence, and the
expression of markers of progression and cell cycle related proteins in
papillomas derived from both strains. Our results showed that while both
strains have a similar papilloma multiplicity and incidence the SENCAR B/Pt
mice have 67% incidence of SCC, compared to 0% in the SSIN. SENCAR B/Pt
papillomas at 30 weeks of promotion have a higher and aberrant expression
of K13, and loss of connexin 26. TGF-beta1 was found to be over-expressed
in the suprabasal and superficial cells in the SENCAR B/Pt papillomas,
while it was only expressed in the superficial cell layer in those derived
from SSIN. The SENCAR B/Pt papillomas also showed an enlarged proliferative
compartment with overexpression of cyclin D1 and PCNA as seen by
immunohistochemistry and Western blot.
ARTICLES
Analysis of two inbred strains of mice derived from the SENCAR stock with different susceptibility to skin tumor progression
University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville 78957, USA.
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