An autoregulatory element maintains HOXA10 expression in endometrial epithelial cells

Objective: HOXA 10 is necessary for endometrial receptivity and regulated by sex steroids. Secretory phase HOXA10 expression increases in endometrial epithelial cells, despite the loss of progesterone receptor. Stromal-epithelial molecular communication likely transmits progesterone signaling from progesterone receptor containing stromal cells to epithelium. Here we investigated an alternative hypothesis, persistent HOXA 10 expression by auto regulation. Study design: Nested segments of the HOXA10 5' regulatory region were cloned into a pGL3-Luciferase reporter construct and tested for HOXA10-induced reporter activity. Direct binding was assayed by electrophoretic mobility shift assay. Results: One 370 base pair element drove reporter gene expression specifically in response to HOXA10 in Ishikawa cells but not in BT-20 cells. This element contained a site that bound HOXA 10 protein. Conclusion: HOXA 10 expression is driven by an autoregulatory element in the 5' regulatory region of the gene. Autoregulation is a novel alternative molecular mechanism by which steroid-induced gene expression can be maintained in the absence of steroid receptors. (C) 2006 Mosby, Inc. All rights reserved.