THE EXPRESSION OF THE GAP JUNCTIONAL PROTEIN CX43 IS RESTRICTED TO PROLIFERATING AND NON DIFFERENTIATED NORMAL AND TRANSFORMED KERATINOCYTES

The passage of specific growth modulating signals through gap junction s may regulate the proliferation and differentiation of human keratino cytes. To investigate this, we correlated the proliferation of normal human keratinocytes and a transformed squamous cell carcinoma cell lin e, SCC4, with the expression of the gap junctional proteins Cx43, 31 a nd 31.1, known to be expressed by keratinocytes. Proliferation was con fined to preconfluent and confluent cultures of normal keratinocytes, falling to undetectable levels once postconfluency was achieved. Cx43, at both the message and protein levels, paralleled these changes, bei ng elevated predominantly in preconfluent and confluent cultures, and downregulated in postconfluency. Similar results were found for Cx31 a nd 31.1 at the message level. In contrast, the proliferation of SCC4 c ells cultured in media supplemented with 5.0% FCS was maintained at a substantial level from preconfluency through 2 weeks postconfluency. C x43, 31, and 31.1 RNA and Cx43 protein expression mirrored the levels of proliferation within SCC4 cultures, Cx26 and 32 were not found in n ormal keratinocytes or SCC4 cells at any stage of differentiation. The se data, illustrating a tight correlation between proliferation and Cx 43, 31 and 31.1 expression, suggest that these connexins may represent proliferation-specific gap junctions within keratinocytes, and may th erefore transmit signals that control keratinocyte division.