CONNEXIN EXPRESSION IN EPIDERMAL-CELL LINES FROM SENCAR MOUSE SKIN TUMORS

Alteration of gap-junctional intercellular communication (GJIC) has lo ng been proposed to be involved in carcinogenesis. Previously, we repo rted that the level of gap junctional intercellular communication in m ouse skin carcinoma cell lines is significantly lower than in papillom a cell lines and normal mouse keratinocytes (Klann et al., Cancer Res 49:699-705, 1989). Here, we present data on expression of the gap-junc tional protein connexins (Cx) 26, Cx31.1, and Cx43 in a comprehensive panel of keratinocyte cell lines representing different stages of mous e skin carcinogenesis and the effect of different conditions of propag ation on Cx phenotype. Northern and western blot analyses and immunost aining showed that all cell lines studied in vitro expressed Cx43 but most did not express Cx31.1 or Cx26. The abundance of Cx43 expression on plasma membranes correlated well with the level of GJIC. In vivo ex pression of Cx43 and Cx26 was strongly increased. Whereas none of tumo rigenic cell lines expressed Cx26 gap junctions in culture, those grow ing as tumors in nude mice began to express Cx26 protein. The comparis on of Cx expression on the keratinocyte membranes in three different g roups of tumors (papillomas and squamous cell and spindle cell carcino mas) clearly revealed that the abundance of Cx43 and Cx26 expression d irectly correlated with the level of tumor differentiation. All studie d tumors were Cx31.1 negative. These results suggest that both Cx expr ession and gap-junction permeability are gradually reduced during the tumor progression stage of mouse skin carcinogenesis. (C) 1996 Wiley-L iss, Inc.