The transcription factor CCAAT/enhancer binding protein (C/EBP)β has been implicated in many developmental processes (for review see Lekstrom-Hines and Xanthopolous 1998) however, no upstream effector of C/EBPβ has, as yet, been identified ( Robinson et al. However, the mechanism of its morphogenic activities remained to be identified. When presented in a polar basal fashion, EPM produced branching morphogenesis, whereas apolar presentation triggered formation of structures with large central lumina. Previously, we used a three-dimensional collagen assay to characterize the function of EPM in normal mammary epithelial cell morphogenesis ( Hirai et al. 1998) and thus is poised to play a role in mammary morphogenesis. In the mammary gland, EPM is present at the surface of both stromal fibroblasts and myoepithelial cells ( Hirai et al. 1998), embryonic lung ( Koshida and Hirai 1997), and pancreatic carcinoma cells ( Lenhert et al. In its capacity as an extracellular morphogen, EPM has been shown to control developmental processes in endothelial ( Oka and Hirai 1996), liver parenchymal ( Hirose et al. 1992 Hirai 1993) a later study also showed that the same gene encoded a member of the syntaxin family ( Bennett et al. Together, our studies demonstrate a role for EPM in luminal morphogenesis through control of C/EBPβ expression.Įpimorphin (EPM) was originally characterized as a stromal cell surface molecule involved in embryonic epithelial morphogenesis ( Hirai et al. 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. 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. 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. Here, we present the molecular mechanism by which EPM mediates luminal morphogenesis. 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.

Western blot results epm