TY - JOUR
T1 - Epimorphin mediates mammary luminal morphogenesis through control of C/EBPβ
AU - Hirai, Yohei
AU - Radisky, Derek
AU - Boudreau, Rosanne
AU - Simian, Marina
AU - Stevens, Mary E.
AU - Oka, Yumiko
AU - Takebe, Kyoko
AU - Niwa, Shinichiro
AU - Bissell, Mina J.
PY - 2001/5/14
Y1 - 2001/5/14
N2 - 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.
AB - 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.
KW - CCAAT/enhancer binding protein
KW - Epithelial-stromal interactions
KW - Mammary morphogenesis
KW - Transcription factor balance
KW - Transgenic mice
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U2 - 10.1083/jcb.153.4.785
DO - 10.1083/jcb.153.4.785
M3 - Article
C2 - 11352939
AN - SCOPUS:0035858879
SN - 0021-9525
VL - 153
SP - 785
EP - 794
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 4
ER -