EXPRESSION AND FUNCTION OF CONNEXIN IN NORMAL AND TRANSFORMED HUMAN KERATINOCYTES IN CULTURE

We have studied the gap junctional intercellular communication (GJIC) of immortalized and tumourigenic human keratinocyte cell lines and of a spontaneously immortalized non-tumourigenic and a highly differentia ting keratinocyte cell line (HaCaT) as the control. In homologous cult ures, the GJIC capacity of five squamous cell carcinoma-derived cell l ines was 1-27% that of the HaCaT cells. Ha-ras-transfected HaCaT cells with tumourigenic potential and an SV40 DNA-immortalized cell line ha d markedly reduced GJIC capacities, Northern analysis and immunohistoc hemistry showed that connexin (Cx) 43 is the major gap junction protei n expressed in the communicating cells. They do not express Cx 26 or 3 2. The low or absent communication observed in certain cell lines was due in some to a lack of Cx 43 gene expression, but in others to aberr ant localization of the gap junction protein. GJIC of these cell lines , as well as that of primary normal human epidermal keratinocytes, was susceptible to 12-O-tetra-decanoylphorbol-13-acetate-mediated inhibit ion. Moreover, GJIC of HaCaT cells and their tumourigenic derivatives is Ca2+-dependent. These results, when compared with those previously obtained for mouse keratinocyte cell lines, reveal that GJIC of human keratinocytes was correlated to the degree of differentiation and is c ontrolled in a similar way to that of murine keratinocytes. Aberrant G JIC seems to be a common feature of human and murine skin carcinogenes is.