This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Makrigiannakis, A. Articles by White, J. Search for Related Content PubMed PubMed Citation Articles by Makrigiannakis, A. Articles by White, J.

Expression of Wilms’ Tumor Suppressor Gene (WT1) in Human Endometrium: Regulation through Decidual Differentiation

Department of Reproductive Science and Medicine (A.Mak., A.Man., G.T., R.M., R.W., J.W.), Imperial College School of Medicine, Hammersmith Hospital, W12 ONN OHS, London, United Kingdom; Medical School of Crete (A.Mak., P.P.), Iraclion, Crete, Greece 7110; and Department of Obstetrics and Gynecology (G.C.), UPENN Medical Center, Philadelphia, Pennsylvania 19104

Address all correspondence and requests for reprints to: Antonis Makrigiannakis, M.D., Ph.D., Department of Pharmacology, University of Crete Medical School, Stavrakia, Iraklion 71110, Greece. E-mail: makrigia{at}med.uoc.gr

Abstract

The Wilms’ tumor suppressor gene (WT1) encodes a zinc-finger containing transcription factor that is selectively expressed in the developing urogenital tract and functions as a tissue-specific developmental regulator. In addition to its gene-regulatory function through DNA binding properties, WT-1 also regulates transcription by formation of protein-protein complexes. These properties place WT-1 as a major regulator of cell growth and differentiation. In view of these observations, we studied WT1 mRNA and protein in human endometrial extracts and in endometrial stromal cells (ESCs) differentiating into decidual cells in vitro, by RT-PCR and Western blotting, respectively. WT1 protein expression was also studied in situ in the proliferative and the secretory phase of the menstrual cycle in the early pregnant state. Analysis by PCR of total RNA prepared from human ESCs demonstrated the presence of WT1 mRNA and four WT1 mRNA splice variants. Western blot analysis of nuclear protein extracts from ESCs yielded one immunoreactive protein of the expected size (approximately 52–54 kDa) recognized by the WT1 antibody. Immunohistochemical staining showed that WT1 protein is localized only to nuclei of human endometrial stromal cells. It remains constant in the proliferative and the secretory phase of the menstrual cycle and is increased remarkably during decidualization in early pregnancy. ESCs decidualized in vitro were investigated for WT-1 expression, which confirmed that decidualizing stimuli (E2, medroxy-progesterone-acetate, and relaxin for 12 d or cAMP and progesterone for 1–4 d) induced WT-1 mRNA (P < 0.05) and increased protein levels (P < 0.05). These data indicate that in humans the WT1 gene is expressed in ESCs and its mRNA and protein levels remain constant in the proliferative and the secretory phase of the menstrual cycle and that WT1 mRNA and protein expression increases significantly in ESCs when these cells differentiate into decidual cells.

This article has been cited by other articles:

				J. D. Graham, M. L. Yager, H. D. Hill, K. Byth, G. M. O'Neill, and C. L. Clarke Altered Progesterone Receptor Isoform Expression Remodels Progestin Responsiveness of Breast Cancer Cells Mol. Endocrinol., November 1, 2005; 19(11): 2713 - 2735. [Abstract] [Full Text] [PDF]

				F. W. Anthony, D. D. Mukhtar, M. A. Pickett, and I. T. Cameron Progesterone Up-Regulates WT1 mRna and Protein, and Alters the Relsative Expression of WT1 Transcripts in Cultured Endometrial Stromal Cells Reproductive Sciences, December 1, 2003; 10(8): 509 - 516. [Abstract] [PDF]

				B. Gurates, S. Sebastian, S. Yang, J. Zhou, M. Tamura, Z. Fang, T. Suzuki, H. Sasano, and S. E. Bulun WT1 and DAX-1 Inhibit Aromatase P450 Expression in Human Endometrial and Endometriotic Stromal Cells J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4369 - 4377. [Abstract] [Full Text] [PDF]