Differential regulation of endothelin secretion and endothelin receptor mRNA levels in JAR, JEG-3, and BeWo choriocarcinoma cell lines and in human trophoblasts, their nonmalignant counterpart

Endothelin (ET) secretion and expression of both ET-A and ET-B receptor sub types have been found in a number of primary cancers. The present study tes ted (1) whether choriocarcinoma cells and their nonmalignant counterpart, t he trophoblast, secrete ET-1 and express ET-A and ET-B receptors; (2) wheth er ET-1 secretion and receptor mRNA levels are regulated by the same factor s in nonvascular tissues as in vascular tissues; and (3) whether such regul ation is similar in malignant and nonmalignant cells. All cells secreted ET -1 in similar amounts (similar to0.8 fmol/10(6) cells per 24 h) and secreti on was unaffected by culture and treatment. Whereas ET-B accounted for almo st all (>98%) ET receptor transcripts in the choriocarcinoma cells, the tro phoblasts expressed about 20% ET-A receptor mRNA. During control cultures, ET-B mRNA levels rose in choriocarcinoma, with the greatest relative increa se (6-fold; P < 0.05 vs 9 h) in BeWo, whereas in trophoblasts, ET-A mRNA tr ansiently changed after 24 and 48 h, Treatment with dexamethasone and gluco se did not alter the mRNA levels in all cells. Insulin induced changes (P < 0.05) in ET-B mRNA levels in BeWo (+90 and +60% after 24 and 48 h, respect ively) and JEG-3 (-70%), but not in JAR and trophoblast cells. We conclude that malignant transformation affects the responsiveness of the endothelin receptor system to external stimuli and that the regulation of the endothel in system differs in vascular and nonvascular tissues. (C) 2000 Academic Pr ess.