Identification of TRIM22 as a progesterone-responsive gene in Ishikawa endometrial cancer cells

Progesterone plays important roles in implantation and maintains pregnancy. It antagonizes estrogen-mediated cell proliferation and promotes differentiation in the uterus. The action of progesterone is mediated by specific receptors, namely, the progesterone receptors (PRs). We generated two Ishikawa cell clones stably expressing PR isoform A (PR-A) and identified progesterone-responsive genes using cDNA microarray analysis. Fifteen genes were identified as progesterone-responsive gene candidates by microarray analysis and their progesterone-responsiveness was shown by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis. Out of these 15 genes, we focused on TRIM22. A database search revealed a progesterone response element (PRE) located from the -25 to -11 bp region upstream of TRIM22 exon 1. This PRE had a 1-bp mismatch in the consensus PRE sequence. A chromatin immunoprecipitation assay revealed that the interaction of PR with the TRIM22 PRE region increased in a hormone-dependent manner. The progesterone-dependent enhancer activity of TRIM22 PRE was demonstrated using a luciferase assay. Based on these results, we propose that TRIM22 is a direct target gene of PR and that it can mediate progesterone actions in uterine cells.