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.
Cella
N
N
Friedrich Miescher-Institut, P.O. Box 2543, CH-4002 Basel, Switzerland.
Chiquet-Ehrismann
R
R
Hynes
N E
NE
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D022762:CCAAT-Enhancer-Binding Proteins; D002364:Caseins / Q000235:genetics; D002454:Cell Differentiation; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008894:Milk Proteins; D009687:Nuclear Proteins / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D020033:Protein Isoforms / Q000378:metabolism; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D019063:Tenascin / Q000378:metabolism / Q000494:pharmacology*; D015534:Trans-Activators / Q000378:metabolism
D022762:CCAAT-Enhancer-Binding Proteins; D002364:Caseins; D004268:DNA-Binding Proteins; D007328:Insulin; D008894:Milk Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D050799:STAT5 Transcription Factor; D019063:Tenascin; D015534:Trans-Activators; D003907:Dexamethasone; D011388:Prolactin; D004247:DNA