期刊
MOLECULAR BIOLOGY REPORTS
卷 34, 期 3, 页码 199-206出版社
SPRINGER
DOI: 10.1007/s11033-007-9085-3
关键词
COX-2; CREB; Elk-1; Ets-1; promoter activity; STAT1
Cyclooxygenase-2 (COX-2) expression is associated with many aspects of physiological and pathological conditions, including pancreatic beta-cell dysfunction. Prostaglandin E2 (PGE2) production, as a consequence of COX-2 gene induction, has been reported to impair beta-cell function. The molecular mechanisms involved in the regulation of COX-2 gene expression are not fully understood. In this report, we used pancreatic beta-cells (RINm5F) to explore the potential transcription factors regulating COX-2 promoter activity. Using promoter screening method, we selected several transcription factors in our study. Through luciferase reporter studies, we found that these factors can regulate COX-2 promoter activity in RINm5F cells. Among these factors, cyclic AMP response-element binding protein (CREB), Ets family members Ets-1 and Elk-1 can positively regulate COX-2 promoter activity. On the contrary, signal transducer and activator of transcription 1 (STAT1) plays a negative role on COX-2 promoter. Our findings will be helpful for better understanding the transcriptional regulation of COX-2 in pancreatic beta-cells. Moreover, these transcriptional regulators of COX-2 expression will be potential targets for the prevention of beta-cell damage mediated by PGE2.
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