POSSIBLE MOLECULAR MECHANISM OF LOSS OF HOMOLOGOUS AND HETEROLOGOUS GAP JUNCTIONAL INTERCELLULAR COMMUNICATION IN RAT-LIVER EPITHELIAL-CELLLINES

We have previously characterized a series of rat liver epithelial cell lines that exhibit levels of gap junctional intercellular communicati on (GJIC) which are inversely related to their levels of expression of transformed phenotypes. Cells of the non-tumorigenic line do not comm unicate with their tumorigenic counterparts. We have examined the mole cular mechanisms involved in this loss of homologous and heterologous GJIC, employing a nontumorigenic cell line, IAR 20, and a tumorigenic cell line, IAR 6-1. While both cell lines expressed a transcript codin g for the gap junction protein, connexin 43 (ex 43), and similar level s of ex 43 protein, they exhibited different phosphorylation states of this protein, revealed by Western analysis. Immunohistochemical analy sis showed that the nontumorigenic IAR 20 cell line, but not the tumor igenic IAR 6-1 cells, was able to incorporate ex 43 gap junction plaqu es extensively into their plasma membranes. When IAR 20 and LAR 6-1 ce lls were co-cultured, ex 43 proteins were abundant in IAR 20 cells but IAR 20/IAR 20 cell boundaries were ex 43-positive, while IAR 20/IAR 6 -1 boundaries were negative. The different phosphorylation state of oc 43 may partially explain the low GJIC of the IAR 6-1 cells and inabil ity to communicate with their non-tumorigenic counterparts, but other mechanisms such as cell-cell recognition processes may also be involve d.