Epimorphin mediates mammary luminal morphogenesis through control of C/EBPbeta

We have shown previously that epimorphin (EPM), 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 EPM mediates luminal morphogenesis. Treatm...

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Bibliographic Details
Published in:The Journal of cell biology 2001-05, Vol.153 (4), p.785-794
Main Authors: Hirai, Y, Radisky, D, Boudreau, R, Simian, M, Stevens, M E, Oka, Y, Takebe, K, Niwa, S, Bissell, M J
Format: Article
Language:English
Subjects:
Animals
Breasts
CCAAT-Enhancer-Binding Proteins - metabolism
Cell Communication - physiology
Cellular biology
Epithelial Cells - cytology
Epithelial Cells - physiology
Female
Lactation - physiology
Mammary Glands, Animal - cytology
Mammary Glands, Animal - growth & development
Mammary Glands, Animal - physiology
Membrane Glycoproteins - analysis
Membrane Glycoproteins - genetics
Membrane Glycoproteins - metabolism
Mice
Mice, Transgenic
Milk Proteins - genetics
Proteins
Rodents
Stromal Cells - cytology
Stromal Cells - physiology
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Summary:We have shown previously that epimorphin (EPM), 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 EPM mediates luminal morphogenesis. Treatment of cells with EPM to induce lumen formation greatly increases the overall expression of transcription factor CCAAT/enhancer binding protein (C/EBP)beta and alters the relative expression of its two principal isoforms, LIP and LAP. These alterations were shown to be essential for the morphogenetic activities, since constitutive expression of LIP was sufficient to produce lumen formation, whereas constitutive expression of LAP blocked EPM-mediated luminal morphogenesis. Furthermore, in a transgenic mouse model in which EPM 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 EPM in luminal morphogenesis through control of C/EBPbeta expression.
ISSN:0021-9525
1540-8140