A regulatory mechanism of mouse kallikrein 1 gene expression by estrogen

Abstract

Tissue kallikrein 1 (Klk1) is a serine protease that degrades several proteins including insulin-like growth factor binding protein-3 and extracellular matrix molecules. Klk1 mRNA expression in the mouse uterus was increased by estradiol-17β (E2). The present study aimed to clarify the regulatory mechanism for Klk1 expression by estrogen. The promoter analysis of the 5′-flanking region of Klk1 showed that the minimal promoter of Klk1 existed in the −136/+24 region, and the estrogen-responsive region in the −433/-136 region. Tamoxifen increased Klk1 mRNA expression and the promoter activity, suggesting the involvement of AP-1 sites. Site-directed mutagenesis for the putative AP-1 sites in the −433/-136 region showed that the two putative AP-1 sites were involved in the regulation of Klk1 expression. Binding of estrogen receptor α (ERα) to the −433/-136 region was revealed by Chip assay. These results indicated that ERα bound the two putative AP-1 sites and transactivated Klk1 in the mouse uterus.