Epimorphin mediates mammary luminal morphogenesis through control of C/EBPbeta
We have previously shown that epimorphin, a protein expressed on the surface of myoepithelial and fibroblast cells of the mammary gland, acts as a multifunctional morphogen of mammary epithelial cells. Here, we present the molecular mechanism by which epimorphin mediates luminal morphogenesis. Treatment of cells with epimorphin to induce lumen formation greatly increases the overall expression of transcription factor CCAAT/enhancer binding protein beta (C/EBPbeta) and alters the relative expression of its two principal isoforms, LIP and LAP. These alterations were shown to be essential for the morphogenetic activities, as constitutive expression of LIP was sufficient to produce lumen formation, while constitutive expression of LAP blocked epimorphin-mediated luminal morphogenesis. Furthermore, in a transgenic mouse model in which epimorphin expression was expressed in an apolar fashion on the surface of mammary epithelial cells, we found increased expression of C/EBPbeta, increased relative expression of LIP to LAP, and enlarged ductal lumina. Together, our studies demonstrate a role for epimorphin in luminal morphogenesis through control of C/EBPbeta expression.
- Research Organization:
- Ernest Orlando Lawrence Berkeley National Lab., CA (US)
- Sponsoring Organization:
- USDOE Director, Office of Science. Office of Biological and Environmental Research; National Institutes of Health (NIH); Distinguished Hollaender Postdoctoral fellowship and the Science and Technology Agency of Japan an (US)
- DOE Contract Number:
- AC03-76SF00098
- OSTI ID:
- 793806
- Report Number(s):
- LBNL-49942; R&D Project: 443101; TRN: US200208%%107
- Journal Information:
- The Journal of Cell Biology, Vol. 153, Issue 4; Other Information: Journal Publication Date: May 14, 2001; PBD: 22 Mar 2002
- Country of Publication:
- United States
- Language:
- English
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