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Published online 14 May 2001. doi:10.1083/jcb.153.4.785
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© The Rockefeller University Press, 0021-9525/2001//785 $5.00
The Journal of Cell Biology, Volume 153, Number 4, , 2001 785-794

Original Article

Epimorphin Mediates Mammary Luminal Morphogenesis through Control of C/EBPβ



Yohei Hiraia,b, Derek Radiskya, Rosanne Boudreaua, Marina Simiana, Mary E. Stevensa, Yumiko Okab, Kyoko Takebeb, Shinichiro Niwab, and Mina J. Bissella

a Life Science Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720
b Osaka R&D Laboratory (Yokohama-lab), Sumitomo Electric Industries Ltd., Yokohama 244, Japan
Life Science Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720.(510) 486-5586(510) 486-4365

mjbissell{at}lbl.gov

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)β 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/EBPβ, 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/EBPβ expression.

Key Words: transcription factor balance • mammary morphogenesis • epithelial–stromal interactions • CCAAT/enhancer binding protein • transgenic mice

© 2001 The Rockefeller University Press

M.E. Stevens' present address is Bayer Corp., Berkeley, CA 94701.

Abbreviations used in this paper: C/EBP, CCAAT/enhancer binding protein β; CMV, cytomegalovirus; EPM, epimorphin; MMP, metalloproteinase; rEPM, recombinant EPM; RT, reverse transcription; WAP, whey acidic protein.


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