THE EXPRESSION OF GAP JUNCTIONAL PROTEINS DURING DIFFERENT STAGES OF MOUSE SKIN CARCINOGENESIS

The loss or alteration of gap junctional intercellular communication ( GJIC) has long been proposed to play an important role in the process of carcinogenesis, In this study we examined the expression of three g ap junction proteins, connexins (Cx)26, 43 and 31.1, in mouse hyperpla stic skin, papillomas and squamous cell carcinomas (SCC), Tumors were induced in SENCAR mice by either of two initiation/promotion protocols : 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoyl-phorbol-13- acetate (TPA) or DMBA/benzoyl-peroxide (BzPo), Keratinocytes in adult mouse skin expressed Cx31.1 and Cx43 but did not express Cx26, Skin hy perplasia induced by one topical application of TPA was accompanied by hyperexpression of both Cx26 and Cx43, In addition, TPA significantly inhibited the expression of Cx31.1. After repetitive application of T PA for 3 weeks to initiated mouse skin, a similar Cx profile was found to that after a single TPA application, Connexin 26 and Cx43 were hyp erexpressed in most of the papillomas studied (20-40 weeks after initi ation), However, in some late papillomas, immunostaining revealed a fo cal loss of Cx26, Immunostaining of mouse skin SCC revealed decreased Cx43 and Cx26 levels in 65% and 85% of cases respectively, The high le vels of Cx26 and Cx43 mRNA in most of the SCC did not correlate with t he decreased abundance or disappearance of Cx26 and Cx43 immunoreactiv e spots from tumor plasma membranes, Thus, the expression of these two connexins in SCC was impaired at the post-translation level, Cx31.1 e xpression was strongly inhibited during all stages of carcinogenesis, Taken together, our results suggest that three different connexin gene s are differentially regulated during mouse skin carcinogenesis and th e decrease of connexin expression may be an important marker of skin t umor progression.