TY - JOUR
T1 - Induction of cyclooxygenase-2 in human endometrial stromal cells by malignant endometrial epithelial cells
T2 - Evidence for the involvement of extracellularly regulated kinases and CCAAT/enhancer binding proteins
AU - Tamura, M.
AU - Sebastian, S.
AU - Yang, S.
AU - Gurates, B.
AU - Fang, Z.
AU - Okamura, K.
AU - Bulun, S. E.
PY - 2003/8
Y1 - 2003/8
N2 - 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.
AB - 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.
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U2 - 10.1677/jme.0.0310095
DO - 10.1677/jme.0.0310095
M3 - Article
C2 - 12914528
AN - SCOPUS:0041852764
SN - 0952-5041
VL - 31
SP - 95
EP - 104
JO - Journal of Molecular Endocrinology
JF - Journal of Molecular Endocrinology
IS - 1
ER -