Regulation of gap junctional communication in Syrian hamster embryo cells by retinoic acid and 12-O-tetradecanoylphorbol-13-acetate.
Retinoids enhance the frequency of Syrian hamster embryo (SHE) cell colonies with transformed morphology in a similar way to tumor-promoting phorbol esters. The present study shows that retinoids are also potent inhibitors of gap junctional intercellular communication in SHE cells at noncytotoxic concentrations. This is an apparent contrast to the results observed in transformation systems using the mouse cell lines C3H10T1/2 and BALB/c 3T3, where retinoids have been found to reduce the induction of transformation, and also to enhance gap junctional cell communication. Retinoids are thus potent modulators of transformation and cell communication in three transformation systems. For all three cell types, enhancement of communication by retinoids is related to reduced transformation, and inhibition of communication to enhanced induction of transformation. Communication in the SHE cells is completely blocked following 1 h exposure to 30 microM retinoic acid, while concentrations of 0.3-15 microM results in a gradual down-regulation of communication during 1-5 h exposure. Removal of retinoic acid results in complete restoration of communication to control values within a few hours. Primary SHE cells and the cell line BPNi show similar sensitivity for inhibition of communication after exposure to retinoic acid, while BPNi cells are far more sensitive to inhibition of communication by 12-O-tetradecanoylphorbol-13-acetate (TPA) than primary SHE cells. Retinoic acid does not induce inhibition of epidermal growth factor binding, potentiate adenylate cyclase activation or enhance arachidonic acid release, as does TPA, suggesting different mechanisms of action.
Rivedal
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Laboratory for Environmental and Occupational Cancer, Norwegian Radium Hospital, Oslo.
Sanner
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D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line; D002461:Cell Line, Transformed / Q000187:drug effects; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D007365:Intercellular Junctions / Q000187:drug effects*; D008647:Mesocricetus; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*
D016718:Arachidonic Acid; D014212:Tretinoin; D004815:Epidermal Growth Factor; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate