Endocrinology, Vol 137, 2225-2231, Copyright © 1996 by Endocrine Society

ARTICLES

Human endometrial fibroblasts immortalized by simian virus 40 large T antigen differentiate in response to a decidualization stimulus

JJ Brosens, S Takeda, CH Acevedo, MP Lewis, PL Kirby, EK Symes, T Krausz, A Purohit, B Gellersen and JO White
Institute of Obstetrics and Gynecology, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.

Human endometrial fibroblasts have been immortalized by infection with simian virus 40 large T antigen and established as a permanent cell line, St-2. Biochemical differentiation of this cell line has been demonstrated by the ability of a decidualizing stimulus, 8-bromo-cAMP plus medroxyprogesterone acetate (MPA), to induce PRL secretion and increase the enzymatic activity of estrone sulfatase. MPA, alone or in combination with estradiol, was unable to elicit this response, but potentiated the effect of 8-bromo-cAMP on PRL production and estrone sulfatase activity. The increase in PRL protein was accompanied by an increase in PRL messenger RNA and increased expression of the insulin- like growth factor-binding protein-1 messenger RNA. The St-2 cell PRL transcript was larger than the pituitary PRL transcript, suggesting its initiation from the distal, nonpituitary, PRL promoter. This was confirmed by reverse transcription-PCR analysis of PRL transcripts using primers specific for the additional sequences present only in the 5'-untranslated region of RNA initiated from the distal promoter. Transient transfection of a reporter construct containing 3000 bp of DNA 5' to the decidual-specific promoter of the human PRL gene demonstrated that cAMP was capable of activating this distal promoter in St-2 cells. In conclusion, this novel cell line provides an interesting new model in which to pursue aspects of biochemical differentiation of human endometrium in vitro.

This article has been cited by other articles:

				O. Eyal, J.-B. Jomain, C. Kessler, V. Goffin, and S. Handwerger Autocrine Prolactin Inhibits Human Uterine Decidualization: A Novel Role for Prolactin Biol Reprod, May 1, 2007; 76(5): 777 - 783. [Abstract] [Full Text] [PDF]

				P. Chapdelaine, J. Kang, S. Boucher-Kovalik, N. Caron, J. P. Tremblay, and M. A. Fortier Decidualization and maintenance of a functional prostaglandin system in human endometrial cell lines following transformation with SV40 large T antigen Mol. Hum. Reprod., May 1, 2006; 12(5): 309 - 319. [Abstract] [Full Text] [PDF]

				E. R. Hugo, T. D. Brandebourg, C. E. S. Comstock, K. S. Gersin, J. J. Sussman, and N. Ben-Jonathan LS14: A Novel Human Adipocyte Cell Line that Produces Prolactin Endocrinology, January 1, 2006; 147(1): 306 - 313. [Abstract] [Full Text] [PDF]

				O. BARTSCHA and R. IVELL Relaxin and Phosphodiesterases Collaborate during Decidualization Ann. N.Y. Acad. Sci., December 1, 2004; 1030(1): 479 - 492. [Abstract] [Full Text] [PDF]

				O. Bartsch, B. Bartlick, and R. Ivell Phosphodiesterase 4 Inhibition Synergizes with Relaxin Signaling to Promote Decidualization of Human Endometrial Stromal Cells J. Clin. Endocrinol. Metab., January 1, 2004; 89(1): 324 - 334. [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]

				I. Y. H. Mak, J. J. Brosens, M. Christian, F. A. Hills, L. Chamley, L. Regan, and J. O. White Regulated Expression of Signal Transducer and Activator of Transcription, Stat5, and its Enhancement of PRL Expression in Human Endometrial Stromal Cells in Vitro J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2581 - 2588. [Abstract] [Full Text] [PDF]

				M. Christian, Y. Pohnke, R. Kempf, B. Gellersen, and J. J. Brosens Functional Association of PR and CCAAT/Enhancer-Binding Protein {beta} Isoforms: Promoter-Dependent Cooperation between PR-B and Liver-Enriched Inhibitory Protein, or Liver-Enriched Activatory Protein and PR-A in Human Endometrial Stromal Cells Mol. Endocrinol., January 1, 2002; 16(1): 141 - 154. [Abstract] [Full Text] [PDF]

				A. Zeitvogel, R. Baumann, and A. Starzinski-Powitz Identification of an Invasive, N-Cadherin-Expressing Epithelial Cell Type in Endometriosis Using a New Cell Culture Model Am. J. Pathol., November 1, 2001; 159(5): 1839 - 1852. [Abstract] [Full Text] [PDF]

				R. Telgmann, J.J. Brosens, K. Kappler-Hanno, R. Ivell, and C. Kirchhoff Epididymal epithelium immortalized by simian virus 40 large T antigen: a model to study epididymal gene expression Mol. Hum. Reprod., October 1, 2001; 7(10): 935 - 945. [Abstract] [Full Text] [PDF]

				M. Christian, P. Marangos, I. Mak, J. McVey, F. Barker, J. White, and J. J. Brosens Interferon-{{gamma}} Modulates Prolactin and Tissue Factor Expression in Differentiating Human Endometrial Stromal Cells Endocrinology, July 1, 2001; 142(7): 3142 - 3151. [Abstract] [Full Text] [PDF]

				K. Watanabe, C. A. Kessler, C. J. Bachurski, Y. Kanda, B. D. Richardson, J. Stanek, S. Handwerger, and A. K. Brar Identification of a Decidua-Specific Enhancer on the Human Prolactin Gene with Two Critical Activator Protein 1 (AP-1) Binding Sites Mol. Endocrinol., April 1, 2001; 15(4): 638 - 653. [Abstract] [Full Text]

				J. J. Brosens, N. Hayashi, and J. O. White Progesterone Receptor Regulates Decidual Prolactin Expression in Differentiating Human Endometrial Stromal Cells Endocrinology, October 1, 1999; 140(10): 4809 - 4820. [Abstract] [Full Text]

				A. Akoum, J. Lavoie, R. Drouin, C. Jolicoeur, A. Lemay, R. Maheux, and E. W. Khandjian Physiological and Cytogenetic Characterization of Immortalized Human Endometriotic Cells Containing Episomal Simian Virus 40 DNA Am. J. Pathol., April 1, 1999; 154(4): 1245 - 1257. [Abstract] [Full Text] [PDF]

				A. K. BRAR, S. HANDWERGER, C. A. KESSLER, and B. J. ARONOW Gene induction and categorical reprogramming during in vitro human endometrial fibroblast decidualization Physiol Genomics, December 21, 2001; 7(2): 135 - 148. [Abstract] [Full Text] [PDF]