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S Hombach-Klonisch Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada
Department of Immunology, Martin Luther University, Halle-Wittenberg, Germany
Department of Obstetrics and Gynecology, University of Aberdeen, Aberdeen, UK
Department of Anatomy, RWTH Aachen, Germany
Department of Dermatology, RWTH Aachen, Germany
Department of Analytical and Environmental Chemistry, Martin Luther University, Halle-Wittenberg, Germany
Department of Pathology, Martin Luther University, Halle-Wittenberg, Germany

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A Kehlen Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada
Department of Immunology, Martin Luther University, Halle-Wittenberg, Germany
Department of Obstetrics and Gynecology, University of Aberdeen, Aberdeen, UK
Department of Anatomy, RWTH Aachen, Germany
Department of Dermatology, RWTH Aachen, Germany
Department of Analytical and Environmental Chemistry, Martin Luther University, Halle-Wittenberg, Germany
Department of Pathology, Martin Luther University, Halle-Wittenberg, Germany

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P A Fowler Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada
Department of Immunology, Martin Luther University, Halle-Wittenberg, Germany
Department of Obstetrics and Gynecology, University of Aberdeen, Aberdeen, UK
Department of Anatomy, RWTH Aachen, Germany
Department of Dermatology, RWTH Aachen, Germany
Department of Analytical and Environmental Chemistry, Martin Luther University, Halle-Wittenberg, Germany
Department of Pathology, Martin Luther University, Halle-Wittenberg, Germany

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B Huppertz Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada
Department of Immunology, Martin Luther University, Halle-Wittenberg, Germany
Department of Obstetrics and Gynecology, University of Aberdeen, Aberdeen, UK
Department of Anatomy, RWTH Aachen, Germany
Department of Dermatology, RWTH Aachen, Germany
Department of Analytical and Environmental Chemistry, Martin Luther University, Halle-Wittenberg, Germany
Department of Pathology, Martin Luther University, Halle-Wittenberg, Germany

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J F Jugert Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada
Department of Immunology, Martin Luther University, Halle-Wittenberg, Germany
Department of Obstetrics and Gynecology, University of Aberdeen, Aberdeen, UK
Department of Anatomy, RWTH Aachen, Germany
Department of Dermatology, RWTH Aachen, Germany
Department of Analytical and Environmental Chemistry, Martin Luther University, Halle-Wittenberg, Germany
Department of Pathology, Martin Luther University, Halle-Wittenberg, Germany

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G Bischoff Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada
Department of Immunology, Martin Luther University, Halle-Wittenberg, Germany
Department of Obstetrics and Gynecology, University of Aberdeen, Aberdeen, UK
Department of Anatomy, RWTH Aachen, Germany
Department of Dermatology, RWTH Aachen, Germany
Department of Analytical and Environmental Chemistry, Martin Luther University, Halle-Wittenberg, Germany
Department of Pathology, Martin Luther University, Halle-Wittenberg, Germany

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E Schlüter Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada
Department of Immunology, Martin Luther University, Halle-Wittenberg, Germany
Department of Obstetrics and Gynecology, University of Aberdeen, Aberdeen, UK
Department of Anatomy, RWTH Aachen, Germany
Department of Dermatology, RWTH Aachen, Germany
Department of Analytical and Environmental Chemistry, Martin Luther University, Halle-Wittenberg, Germany
Department of Pathology, Martin Luther University, Halle-Wittenberg, Germany

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J Buchmann Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada
Department of Immunology, Martin Luther University, Halle-Wittenberg, Germany
Department of Obstetrics and Gynecology, University of Aberdeen, Aberdeen, UK
Department of Anatomy, RWTH Aachen, Germany
Department of Dermatology, RWTH Aachen, Germany
Department of Analytical and Environmental Chemistry, Martin Luther University, Halle-Wittenberg, Germany
Department of Pathology, Martin Luther University, Halle-Wittenberg, Germany

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T Klonisch Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada
Department of Immunology, Martin Luther University, Halle-Wittenberg, Germany
Department of Obstetrics and Gynecology, University of Aberdeen, Aberdeen, UK
Department of Anatomy, RWTH Aachen, Germany
Department of Dermatology, RWTH Aachen, Germany
Department of Analytical and Environmental Chemistry, Martin Luther University, Halle-Wittenberg, Germany
Department of Pathology, Martin Luther University, Halle-Wittenberg, Germany

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Information on the regulation of steroid hormone receptors and their distinct functions within the human endometrial epithelium is largely unavailable. We have immortalized human primary endometrial epithelial cells (EECs) isolated from a normal proliferative phase endometrium by stably transfecting the catalytic subunit (hTERT) of the human telomerase complex and cultured these hTERT-EECs now for over 350 population doublings. Active hTERT was detected in hTERT-EECs employing the telomerase repeat amplification assay protocol. hTERT-EECs revealed a polarized, non-invasive epithelial phenotype with apical microvilli and production of a basal lamina when grown on a three-dimensional collagen–fibroblast lattice. Employing atomic force microscopy, living hTERT-EECs were shown to produce extracellular matrix (ECM) components and ECM secretion was modified by estrogen and progesterone (P4). hTERT-EECs expressed inducible and functional endogenous estrogen receptor-alpha (ER-alpha) as demonstrated by estrogen response element reporter assays and induction of P4 receptor (PR). P4 treatment down-regulated PR expression, induced MUC-1 gene activity and resulted in increased ER-beta transcriptional activity. Gene activities of cytokines and their receptors interleukin (IL)-6, leukemia inhibitory factor (LIF), IL-11 and IL-6 receptor (IL6-R), LIF receptor and gp130 relevant to implantation revealed a 17 beta-estradiol (E2)-mediated up-regulation of IL-6 and an E2- and P4-mediated up-regulation of IL6-R in hTERT-EECs. Thus, hTERT-EECs may be regarded as a novel in vitro model to investigate the role of human EECs in steroid hormone-dependent normal physiology and pathologies, including implantation failure, endometriosis and endometrial cancer.

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S Hombach-Klonisch Department of Human Anatomy and Cell Science, Department of Immunology, Department of Obstetrics and Gynecology, Department of Anatomy, Department of Dermatology, Department of Analytical and Environmental Chemistry, Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada

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A Kehlen Department of Human Anatomy and Cell Science, Department of Immunology, Department of Obstetrics and Gynecology, Department of Anatomy, Department of Dermatology, Department of Analytical and Environmental Chemistry, Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada

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P A Fowler Department of Human Anatomy and Cell Science, Department of Immunology, Department of Obstetrics and Gynecology, Department of Anatomy, Department of Dermatology, Department of Analytical and Environmental Chemistry, Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada

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B Huppertz Department of Human Anatomy and Cell Science, Department of Immunology, Department of Obstetrics and Gynecology, Department of Anatomy, Department of Dermatology, Department of Analytical and Environmental Chemistry, Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada

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J F Jugert Department of Human Anatomy and Cell Science, Department of Immunology, Department of Obstetrics and Gynecology, Department of Anatomy, Department of Dermatology, Department of Analytical and Environmental Chemistry, Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada

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G Bischoff Department of Human Anatomy and Cell Science, Department of Immunology, Department of Obstetrics and Gynecology, Department of Anatomy, Department of Dermatology, Department of Analytical and Environmental Chemistry, Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada

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E Schlüter Department of Human Anatomy and Cell Science, Department of Immunology, Department of Obstetrics and Gynecology, Department of Anatomy, Department of Dermatology, Department of Analytical and Environmental Chemistry, Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada

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J Buchmann Department of Human Anatomy and Cell Science, Department of Immunology, Department of Obstetrics and Gynecology, Department of Anatomy, Department of Dermatology, Department of Analytical and Environmental Chemistry, Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada

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T Klonisch Department of Human Anatomy and Cell Science, Department of Immunology, Department of Obstetrics and Gynecology, Department of Anatomy, Department of Dermatology, Department of Analytical and Environmental Chemistry, Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada

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