A regulatory mechanism of mouse kallikrein 1 gene expression by estrogen

Takumi Iwasaki; Megumi Tokumori; Misaki Matsubara; Fumiya Ojima; Kana Kamigochi; Sayaka Aizawa; Maho Ogoshi; Atsushi P Kimura; Sakae Takeuchi; Sumio Takahashi

doi:10.1016/j.mce.2023.112044

A regulatory mechanism of mouse kallikrein 1 gene expression by estrogen

Mol Cell Endocrinol. 2023 Nov 1:577:112044. doi: 10.1016/j.mce.2023.112044. Epub 2023 Aug 12.

Authors

Affiliations

¹ Graduate School of Natural Science and Technology, Okayama University, Okayama, 700-8530, Japan.
² Department of Natural Sciences and Biology, Kawasaki Medical School, Kurashiki, 701-0192, Japan.
³ Department of Biological Sciences, Faculty of Science, Hokkaido University, Sapporo, 060-0810, Japan.
⁴ Graduate School of Natural Science and Technology, Okayama University, Okayama, 700-8530, Japan. Electronic address: stakaha@cc.okayama-u.ac.jp.

PMID: 37580010
DOI: 10.1016/j.mce.2023.112044

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.

Keywords: Estradiol; Estrogen receptor; Kallikrein 1; Uterus.