Induction of cyclooxygenase-2 in human endometrial stromal cells by malignant endometrial epithelial cells: Evidence for the involvement of extracellularly regulated kinases and CCAAT/enhancer binding proteins

M. Tamura, S. Sebastian, S. Yang, B. Gurates, Z. Fang, K. Okamura, S. E. Bulun*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

We previously reported that human malignant endometrial epithelial cell conditioned medium (MECM) up-regulated cyclooxygenase (COX)-2 mRNA and protein levels in human normal endometrial stromal cells (ESC). Here we showed that pretreatment with a selective inhibitor of the extracellularly regulated kinase (ERK)1/2 signaling pathway blocked the MECM-induced COX-2 expression in ESC. Transient transfection assays indicated critical roles of a cAMP response element (CRE,-59/-53 bp) and a nuclear factor for interleukin (IL)-6 expression (NF-IL6) site (-132/-124 bp) in the regulation of basal and MECM-induced activity of COX-2 gene promoter in ESC. Employing electrophoretic mobility shift assays, we demonstrated that increased functional binding of CCAAT/enhancer binding protein (C/EBP)α, C/EBPβ and upstream stimulatory factor-2 to the CRE and C/EBPα and C/EBβ to the NF-IL6 site were, at least in part, responsible for MECM-induced COX-2 expression in ESC. Moreover, overexpression of C/EBPα and C/EBPβ significantly induced COX-2 promoter activity in ESC. Collectively, these results suggest that the basal and MECM-induced transcription of the COX-2 gene in ESC is regulated through a combination of the CRE and the NF-IL6 site by functional interactions of C/EBPα and C/EBPβ.

Original languageEnglish (US)
Pages (from-to)95-104
Number of pages10
JournalJournal of Molecular Endocrinology
Volume31
Issue number1
DOIs
StatePublished - Aug 2003

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology

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