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 ent of cells with EPM to induce lumen formation greatly increases the overa ll 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 morphogeneti c activities, since constitutive expression of LIP was sufficient to produc e lu-men formation, whereas constitutive expression of LAP blocked EPM-medi ated luminal morphogenesis. Furthermore, in a transgenic mouse model in whi ch EPM expression was expressed in an apolar fashion on the surface of mamm ary epithelial cells, we found increased expression of C/EBP beta, increase d relative expression of LIP to LAP, and enlarged ductal lumina. Together, our studies demonstrate a role for EPM in luminal morphogenesis through con trol of C/EBP beta expression.