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

Mammary epithelial cell differentiation depends on lactogenic hormones, growth factors, and cell-cell and cell-substrate interactions, all of which modulate transcription factors essential for milk protein gene expression. The CCAAT/enhancer binding protein (C/EBP) family and the signal transducer and activator of transcription 5 (Stat5) have been implicated in mammary epithelial cell growth and differentiation. We have investigated the effects of extracellular matrix components and lactogenic hormones on C/EBP and Stat5 activity. In the mammary gland, tenascin is expressed mainly during embryogenesis 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/EBPalpha levels but 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/EBPalpha and C/EBPbeta protein levels but downregulated the DNA binding activity of the transcriptional repressor C/EBPbetaLIP. Thus, C/EBPalpha and beta are regulated by tenascin and lactogenic hormones in mammary epithelial cells.