Impaired expression and posttranslational processing of connexin 43 and downregulation of gap junctional communication in neoplastic human prostate cells

BACKGROUND. Gap junctional communication (GJC) has been implicated in the c ontrol of cell proliferation. Numerous cancer cells show a decrease or loss of GJC compared to their normal counterparts. Lack of adequate information on the status of gap junctions during prostate neoplasia prompted us to ex amine this form of cancer, which comprises about 14% of male cancer deaths in America. METHODS. Cultured normal human prostate epithelial cells and several differ ent human prostate tumor lines were used in this study. GJC was assayed by dye transfer, whereas Western blot and immunofluorescence methods were used to examine connexin43 (Cx43) levels and the presence of gap junctions, res pectively. RESULTS. Normal human prostate cultures exhibited extensive cell-communicat ion which was completely absent in all the examined tumor cells. This disru pted communication was associated with a decreased expression and an impair ed posttranslational modification of Cx43 in these cells. Abundant immunost aining of gap junctional channels by a Cx43-antibody was observed in normal prostate cells but not in tumor cells. CONCLUSIONS. Our data provide further support for the hypothesis that loss of junctional communication is a critical step in progression to human pros tate neoplasia. (C) 1999 Wiley-Liss, Inc.