HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Munir, I. Articles by Miyamoto, E. Search for Related Content PubMed PubMed Citation Articles by Munir, I. Articles by Miyamoto, E. Agricola Articles by Munir, I. Articles by Miyamoto, E.

Expression of Cyclooxygenase 2 by Prostaglandin E₂ in Human Endometrial Adenocarcinoma Cell Line HEC-1B¹

^a Department of Pharmacology and ^b Department of Obstetrics and Gynecology, Kumamoto University Schoolof Medicine, Kumamoto 860-0811, Japan ^c Department of Obstetrics and Gynecology, Shimane Medical University, Izumo 693-8501, Japan

ABSTRACT

The regulation of expression of cyclooxygenase 2 (COX-2) was investigated by treatment with PGE₂ in human endometrial adenocarcinoma cell line HEC-1B. One µM PGE₂ could stimulate the expression of COX-2 approximately twofold in this cell line. The same concentration of PGE₂ also stimulated activation of mitogen-activated protein kinase (MAP kinase) and protein kinase B (PKB). PGE₂-induced MAP kinase activation was sensitive to a MAP kinase kinase (MEK) inhibitor, PD098059, and a protein kinase A inhibitor, H-89. PD098059 and H-89 also partially inhibited the expression of COX-2 stimulated by PGE₂. PGE₂ could stimulate the activation of PKB, which was sensitive to phosphatidylinositol-3-OH kinase (PI3K) inhibitor, wortmannin. Whereas wortmannin alone partially inhibited the expression of COX-2, a combination of wortmannin and PD098059 totally inhibited PGE₂-mediated COX-2 expression. These results suggest that MAP kinase and PI3K pathways are stimulated with PGE₂, and that both of these pathways are involved in the expression of COX-2. In addition, they also suggest that protein kinase A remains upstream of PGE₂-induced activation of MAP kinase in HEC-1B cells.

FOOTNOTES

First decision: 12 October 1999.

¹ This work was supported in part by Grants-in-Aid for Scientific Research and for Scientific Research on Priority from the Ministry of Education, Science, Sports and Culture, Japan, and by a research grant from the Human Frontier Science Program to E.M. and K.F.

² Correspondence: Eishichi Miyamoto, Department of Pharmacology, Kumamoto University School of Medicine, Honjo 2-2-1, Kumamoto City 860-0811, Japan. FAX: 81 96 373 5078; emiyamot{at}gpo.kumamoto-u.ac.jp

This article has been cited by other articles:

				S. Srisuparp, Z. Strakova, A. Brudney, S. Mukherjee, S. Reierstad, M. Hunzicker-Dunn, and A. T. Fazleabas Signal Transduction Pathways Activated by Chorionic Gonadotropin in the Primate Endometrial Epithelial Cells Biol Reprod, February 1, 2003; 68(2): 457 - 464. [Abstract] [Full Text] [PDF]

				K. J. Sales, A. A. Katz, R. P. Millar, and H. N. Jabbour Seminal plasma activates cyclooxygenase-2 and prostaglandin E2 receptor expression and signalling in cervical adenocarcinoma cells Mol. Hum. Reprod., December 1, 2002; 8(12): 1065 - 1070. [Abstract] [Full Text] [PDF]

				M. Tamura, S. Sebastian, S. Yang, B. Gurates, K. Ferrer, H. Sasano, K. Okamura, and S. E. Bulun Up-regulation of Cyclooxygenase-2 Expression and Prostaglandin Synthesis in Endometrial Stromal Cells by Malignant Endometrial Epithelial Cells. A PARACRINE EFFECT MEDIATED BY PROSTAGLANDIN E2 AND NUCLEAR FACTOR-kappa B J. Biol. Chem., July 12, 2002; 277(29): 26208 - 26216. [Abstract] [Full Text] [PDF]