Epimorphin Functions as a Key Morphoregulator for Mammary Epithelial Cells

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Hepatocyte growth factor (HGF) and EGF have been reported to promote branching morphogenesis of mammary epithelial cells. We now show that it is epimorphin that is primarily responsible for this phenomenon. In vivo, epimorphin was detected in the stromal compartment but not in lumenal epithelial cells of the mammary gland; in culture, however, a subpopulation of mammary epithelial cells produced significant amounts of epimorphin. When epimorphin-expressing epithelial cell clones were cultured in collagen gels they displayed branching morphogenesis in the presence of HGF, EGF, keratinocyte growth factor, or fibroblast growth factor, a process that was inhibited by anti-epimorphin but not ... continued below

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Hirai, H.; Lochter, A.; Galosy, S.; Koshida, S.; Niwa, S. & Bissell, M.J. October 13, 1997.

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Hepatocyte growth factor (HGF) and EGF have been reported to promote branching morphogenesis of mammary epithelial cells. We now show that it is epimorphin that is primarily responsible for this phenomenon. In vivo, epimorphin was detected in the stromal compartment but not in lumenal epithelial cells of the mammary gland; in culture, however, a subpopulation of mammary epithelial cells produced significant amounts of epimorphin. When epimorphin-expressing epithelial cell clones were cultured in collagen gels they displayed branching morphogenesis in the presence of HGF, EGF, keratinocyte growth factor, or fibroblast growth factor, a process that was inhibited by anti-epimorphin but not anti-HGF antibodies. The branch length, however, was roughly proportional to the ability of the factors to induce growth. Accordingly, epimorphin-negative epithelial cells simply grew in a cluster in response to the growth factors and failed to branch. When recombinant epimorphin was added to these collagen gels, epimorphin-negative cells underwent branching morphogenesis. The mode of action of epimorphin on morphogenesis of the gland, however, was dependent on how it was presented to the mammary cells. If epimorphin was overexpressed in epimorphin-negative epithelial cells under regulation of an inducible promoter or was allowed to coat the surface of each epithelial cell in a nonpolar fashion, the cells formed globular, alveoli-like structures with a large central lumen instead of branching ducts. This process was enhanced also by addition of HGF, EGF, or other growth factors and was inhibited by epimorphin antibodies. These results suggest that epimorphin is the primary morphogen in the mammary gland but that growth factors are necessary to achieve the appropriate cell numbers for the resulting morphogenesis to be visualized.

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  • Journal Name: Journal of Cell Biology; Journal Volume: 140; Journal Issue: 1; Related Information: Journal Publication Date: 1/12/1998

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  • Report No.: LBNL-41888
  • Grant Number: DE-AC02-05CH11231
  • Office of Scientific & Technical Information Report Number: 1003815
  • Archival Resource Key: ark:/67531/metadc832998

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  • October 13, 1997

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  • May 19, 2016, 3:16 p.m.

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  • June 16, 2016, 12:33 p.m.

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Hirai, H.; Lochter, A.; Galosy, S.; Koshida, S.; Niwa, S. & Bissell, M.J. Epimorphin Functions as a Key Morphoregulator for Mammary Epithelial Cells, article, October 13, 1997; Berkeley, California. (digital.library.unt.edu/ark:/67531/metadc832998/: accessed September 24, 2018), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT Libraries Government Documents Department.