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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Tamura, M; Sebastian, S; Yang, S; Gurates, B; Fang, Z; Okamura, K; Bulun, SE

Published Date

  • 2003

Published In

  • Journal of Molecular Endocrinology

Volume / Issue

  • 31 / 1

Start / End Page

  • 95 - 104

PubMed ID

  • 12914528

Digital Object Identifier (DOI)

  • 10.1677/jme.0.0310095