Skip to main content
Article thumbnail
Location of Repository

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

By Katya Chobotova, Mary-Elizabeth Muchmore, Janet Carver, Hyung-J Yoo, Sanjiv Manek, William J. Gullick, David Barlow and Helen J. Mardon

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

Topics: Q, RC0254
Publisher: Endocrine Society
Year: 2002
OAI identifier: oai:kar.kent.ac.uk:3990

Suggested articles

Citations

  1. (1991). A heparin-binding growth factor secreted by macrophage-like cells that is related to EGF.
  2. (1994). A specific inhibitor of epidermal growth factor receptor tyrosine kinase.
  3. (1996). Activation of epidermal growth factor receptor tyrosine phosphorylation by tumor necrosis factor correlates with loss of cytotoxic activity.
  4. (1995). Changes in epidermal growth factor receptor and the levels of its ligands during menstrual cycle in human endometrium.
  5. (1993). Cloning cell surface molecules by transient expression in mammalian cells.
  6. (1990). Down-modulation of epidermal growth factor receptor affinity in fibroblasts treated with interleukin 1 or tumor necrosis factor is associated with phosphorylation at a site other than threonine 654.
  7. (1998). Dynamic expression and activation of ErbB receptors in the developing mouse mammary gland.
  8. (1989). Early events in the antiproliferative action of tumor necrosis factor are similar to the early events in epidermal growth factor stimulation.
  9. (1992). Enhancement of epidermal growth factor receptor expression on glioma cells by recombinant tumor necrosis factor .
  10. (1991). Epidermal growth factor in human endometrium: proliferative effects in culture and immunocytochemical localization in normal and endometriotic tissues. Hum Reprod
  11. (1989). Epidermal growth factor receptor expression in normal and malignant endometrium.
  12. (1998). Expression of the c-erbB4/HER4 protein and mRNA in normal human fetal and adult tissues and in a survey of nine solid tumour types.
  13. (1994). Expression of the genes for the epidermal growth factor receptor and its ligands in porcine oviduct and endometrium.
  14. (1993). Expression of tumor necrosis factor- and its mRNA in the endometrial mucose during the menstrual cycle.
  15. (1994). Heparin-binding EGF-like growth factor, which acts as the diphtheria toxin receptor, forms a complex with membrane protein DRAP27/ CD9, which up-regulates functional receptors and diphtheria toxin sensitivity.
  16. (1993). Heparin-binding EGF-like growth factor: characterization of rat and mouse cDNA clones, protein domain conservation across species, and transcript expression in tissues.
  17. (1997). Heparin-binding EGF-like growth factor. Biochim Biophys Acta 1333:F179–199 balt1/eg-jcem/eg-jcem/eg1202/eg9038-02a harringt
  18. (1994). Heparin-binding epidermal growth factor-like growth factor is differentially regulated by progesterone and estradiol in rat uterine epithelial and stromal cells.
  19. (1994). Implantation and the placenta: key pieces of the development puzzle.
  20. (1993). Inverse regulation of human ERBB2 and epidermal growth factor receptors by tumor necrosis factor .
  21. (1992). Isolation and purification of human endometrial stromal and glandular cells using immuno-magnetic microspheres. Hum Reprod 7:156–161
  22. (1999). Low temperature, heat-mediated antigen retrival (LTHMAR) on archival endometrial sections.
  23. (1995). Membrane-anchored heparinbinding EGF-like growth factor (HB-EGF) and diphtheria toxin receptorassociated protein (DRAP27)/CD9 form a complex with integrin 31 at cellcell contact sites.
  24. (1999). Neuregulin activation of ErbB receptors in vascular endothelium leads to angiogenesis.
  25. (1997). Peptide growth factors and preimplantation development. Hum Reprod Update 3:137–157
  26. (2001). Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase.
  27. (1995). Signals and molecular pathways involved in apoptosis, with special emphasis on human endometrium. Hum Reprod Update 1:303–323 balt1/eg-jcem/eg-jcem/eg1202/eg9038-02a harringt
  28. (1993). The effect of growth factors on the proliferation of human endometrial stromal cells in culture.
  29. (2001). The eighth FIII domain of human fibronectin promotes integrin 51 binding via stabilization of the ninth FIII domain.
  30. (1997). The membranebound form of heparin-binding epidermal growth factor-like growth factor promotes survival of cultured renal epithelial cells.
  31. (1999). The shedding of membrane-anchored heparin-binding epidermal-like growth factor is regulated by the Raf/mitogen-activated protein kinase cascade and by cell adhesion and spreading.
  32. (1996). The signals and molecular pathways involved in human menstruation, a unique process of tissue destruction and remodelling. Mol Hum Reprod 2:77–92
  33. (1992). Tissue distribution of mRNA for heparin-binding epidermal growth factor.
  34. (1996). Tumor necrosis factors: developments during the last decade.
  35. (1998). Vascular endothelial growth factor induces heparin-binding epidermal growth factor-like growth factor in vascular endothelial cells [published erratum appears in

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.