Differential effects of TPA and retinoic acid on cell-cell communication in human bronchial epithelial cells.

Understanding how normal and immortalized bronchial epithelial cells respond to modulators of gap junctional communication will increase our understanding of the process of tumor promotion. In the present study we compared to effects of retinoic acid (RA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) on the rate of fluorescent dye transfer via gap junctions in primary human tracheo-bronchial epithelial cells (TBE) and SV40 large T-antigen immortalized, non-tumorigenic bronchial epithelial cells (BEAS-2B). RA in the physiological range (0.001-1 microM) inhibited cell proliferation (DNA synthesis, mitotic index) more in primary TBE cells than BEAS-2B cells. Also in RA-treated cells, decreased cell proliferation was coupled to decreased gap junctional communication (GJC) in TBE but not in BEAS-2B cells. TPA strongly suppressed GJC and proliferation in primary TBE cells, whereas BEAS-2B exhibited increased GJC and retained a significant fraction of cells undergoing DNA synthesis. Our studies show that an uncoupling of GJC and cell proliferation is associated with a differential response to the growth inhibitory effects of RA and phorbol esters in immortalized compared to primary human bronchial epithelial cells.