The mitogenic potential of heparin-binding epidermal growth factor in the human endometrium is mediated by the epidermal growth factor receptor and is modulated by tumor necrosis factor-alpha

Chobotova, Katya and Muchmore, Mary-Elizabeth and Carver, Janet and Yoo, Hyung-J and Manek, Sanjiv and Gullick, William J. and Barlow, David and Mardon, Helen J. (2002) The mitogenic potential of heparin-binding epidermal growth factor in the human endometrium is mediated by the epidermal growth factor receptor and is modulated by tumor necrosis factor-alpha. Journal of Clinical Endocrinology and Metabolism, 87 (12). pp. 5769-5777. ISSN 0021-972X . (Full text available)

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http://dx.doi.org/10.1210/jc.2002-020069

Abstract

Heparin-binding epidermal growth factor (HB-EGF), a member of the epidermal growth factor (EGF) family, is implicated in a variety of biological processes, including reproduction. Previous studies describe increased levels of HB-EGF in the human endometrium during the midsecretory stage of the menstrual cycle, suggesting a function for HB-EGF in implantation of the human blastocyst. Here we have investigated the expression and function of the soluble and transmembrane forms of HB-EGF in the human endometrium. We show that the expression of the transmembrane form of HB-EGF in the human endometrium is modulated according to the stage of the menstrual cycle. We present data demonstrating that both the soluble and transmembrane forms of HB-EGF induce DNA synthesis in human endometrial stromal cells. Furthermore, TNFalpha has a cooperative effect on HB-EGF, EGF, TGFalpha, and betacellulin-induced DNA synthesis in stromal cells, suggesting roles for the EGF family and TNFalpha in regeneration and maturation of human endometrium. Induction of DNA synthesis by HB-EGF and its modulation by TNFalpha in endometrial stromal cells are mediated by the EGF receptor and not the HB-EGF receptor ErbB4. Our data suggest key functions for HB-EGF, TNFalpha, and the EGF receptor in endometrial maturation, via autocrine/paracrine and juxtacrine pathways, in preparation for embryo implantation.

Item Type: Article
Uncontrolled keywords: Adult Cells, Cultured DNA/biosynthesis Endometrium/cytology/*physiology Epidermal Growth Factor/*physiology Female Humans Intercellular Signaling Peptides and Proteins/physiology Menstrual Cycle/metabolism Middle Aged Mitogens/*physiology Phosphorylation Receptor, Epidermal Growth Factor/metabolism/*physiology Solubility Stromal Cells/metabolism Transforming Growth Factor alpha/physiology Tumor Necrosis Factor-alpha/*physiology
Subjects: Q Science
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences > Biomedical Research Group
Depositing User: Bill Gullick
Date Deposited: 12 Jun 2008 08:58
Last Modified: 02 Jun 2014 15:20
Resource URI: http://kar.kent.ac.uk/id/eprint/3990 (The current URI for this page, for reference purposes)
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