GAP-JUNCTIONAL COMMUNICATION IN NORMAL AND NEOPLASTIC PROSTATE EPITHELIAL CELLS AND ITS REGULATION BY CAMP

Cap-junctional communication and expression of gap junction-forming pr oteins were investigated in normal human prostate epithelial cells and in several malignant prostate cell lines. In comparison with normal c ells, gap-junctional communication in malignant cells, as assayed by t he transfer of 443-Da fluorescent tracer Lucifer yellow, was either re duced or not detected. Malignant cells expressed mRNA transcripts for connexin (Cx) 43, whereas normal cells expressed mRNA transcripts for Cx32 and Cx40, in both normal and malignant cells, gap-junctional comm unication was enhanced twofold to fivefold by treatment with forskolin , an agent known to increase intracellular levels of cAMP, Immunocytoc hemical staining with a Cx43-specific antibody revealed that in malign ant cells this enhancement correlated with the number of gap junctions and occurred without any qualitative or quantitative alteration in Cx 43 mRNA or protein. Moreover, western blot analyses showed that both c ontrol and forskolin-treated malignant cells expressed only one form o f Cx43. Our data suggest that gap-junctional communication in both nor mal and malignant prostate cells may be regulated by hormones that wor k via a cAMP-dependent signal transduction pathway. Thus, both normal and malignant cells offer a new experimental model system in which int eractions between a hormonal form of cellular communication and interc ellular communication mediated via gap junctions can be studied. (C) 1 996 Wiley-Liss, Inc.