Lactogenic hormones and tenascin-C regulate C/EBP alpha and beta in mammary epithelial cells

Mammary epithelial cell differentiation depends on lactogenic hormones, gro wth factors, and cell-cell and cell-substrate interactions, all of which mo dulate transcription factors essential for milk protein gene expression. Th e CCAAT/enhancer binding protein (C/EBP) family and the signal transducer a nd activator of transcription 5 (Stat5) have been implicated in mammary epi thelial cell growth and differentiation. We have investigated the effects o f extracellular matrix components and lactogenic hormones on WEEP and Stat5 activity. In the mammary gland, tenascin is Expressed mainly during embryo genesis and carcinogenesis and in cell culture tenascin downregulates beta- casein gene expression. In HC11 mammary cells, we found that tenascin, but not laminin or fibronectin, specifically downregulated C/EBP alpha levels b ut had no effect on Stat5 amount, or DNA binding activity. Furthermore, we found that the lactogenic hormones, glucocorticoids, prolactin, and insulin , had no effect on C/EBP alpha and C/EBP beta protein levels but downregula ted the DNA binding activity of the transcriptional repressor C/EBP beta LI P. Thus, C/EBP alpha and beta are regulated by tenascin and lactogenic horm ones in mammary epithelial cells. (C) 2000 Wiley-Liss, Inc.