Regular Article
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

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Abstract

Endothelin (ET) secretion and expression of both ET-A and ET-B receptor subtypes have been found in a number of primary cancers. The present study tested (1) whether choriocarcinoma cells and their nonmalignant counterpart, the trophoblast, secrete ET-1 and express ET-A and ET-B receptors; (2) whether ET-1 secretion and receptor mRNA levels are regulated by the same factors in nonvascular tissues as in vascular tissues; and (3) whether such regulation is similar in malignant and nonmalignant cells. All cells secreted ET-1 in similar amounts (∼0.8 fmol/106 cells per 24 h) and secretion was unaffected by culture and treatment. Whereas ET-B accounted for almost all (>98%) ET receptor transcripts in the choriocarcinoma cells, the trophoblasts expressed about 20% ET-A receptor mRNA. During control cultures, ET-B mRNA levels rose in choriocarcinoma, with the greatest relative increase (6-fold; P < 0.05 vs 0 h) in BeWo, whereas in trophoblasts, ET-A mRNA transiently changed after 24 and 48 h. Treatment with dexamethasone and glucose 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, respectively) 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 endothelin system differs in vascular and nonvascular tissues.

References (44)

  • J.J. Yohn et al.

    Biochem. Biophys. Res. Commun.

    (1994)
  • S. Moraitis et al.

    Eur. J. Cancer

    (1997)
  • K.V. Patel et al.

    Mol. Cell. Endocrinol.

    (1997)
  • S.C. Shorter et al.

    Placenta

    (1993)
  • A. Beham et al.

    Placenta

    (1988)
  • G.O. Babalola et al.

    Dev. Biol.

    (1990)
  • A.M. Mitchell et al.

    Placenta

    (1995)
  • J.C. Monge et al.

    J. Biol. Chem.

    (1995)
  • P. Nambi et al.

    J. Biol. Chem.

    (1992)
  • K. Shibata et al.

    Brain Res.

    (1995)
  • M. Saito et al.

    Eur. J. Pharmacol.

    (1996)
  • I. Nakamura et al.

    Peptides

    (1997)
  • M. Yanagisawa et al.

    Nature

    (1988)
  • M. Cervar et al.

    J. Invest. Med.

    (1996)
  • M. Kusuhara et al.

    Cancer Res.

    (1990)
  • M. Shichiri et al.

    J. Clin. Invest.

    (1991)
  • A. Bagnato et al.

    Clin. Cancer Res.

    (1995)
  • A. Bagnato et al.

    Cancer Res.

    (1997)
  • J.B. Nelson et al.

    Cancer Res.

    (1996)
  • K. Benirschke

    Choriocarcinoma

  • M.P. Schrey et al.

    Cancer Res.

    (1992)

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