CCAAT/enhancer binding protein beta (C/EBPbeta)-2 transforms normal mammary epithelial cells and induces epithelial to mesenchymal transition in culture.
The transcription factor CCAAT/enhancer binding protein (C/EBP)beta is critical for normal growth and differentiation of the mammary gland. The intronless C/EBPbeta gene encodes a single mRNA that produces three protein isoforms, C/EBPbeta-1, -2, and -3, which share a common basic-leucine zipper domain at their C-terminus, but are distinguished at their N-termini by the in-frame methionine codon used to initiate translation. Although C/EBPbeta-1 and -2 are both transactivators, they likely perform distinct functions in mammary epithelial cells. C/EBPbeta-1 is the only isoform detected in normal human mammary tissue. In breast cancer cell lines, C/EBPbeta-1 is absent, and the C/EBPbeta-2 transactivator is expressed. Moreover, our data suggest that C/EBPbeta-2 is upregulated in human primary breast tumors. To assess C/EBPbeta-2's ability to participate in the transformation process, we generated recombinant retrovirus selectively encoding epitope-tagged C/EBPbeta-2. Strikingly, 10 days after infecting a normal human mammary epithelial cell line (MCF10A) with C/EBPbeta-2 virus, transformed subcultures were readily generated. Specifically, C/EBPbeta-2-overexpressing MCF10A cells form foci, gain anchorage independence, express markers associated with having undergone an epithelial-to-mesenchymal transition, and acquire an invasive phenotype. These studies, and our previous observations, provide supportive evidence that deregulated expression of C/EBPbeta-2 contributes to malignant conversion of the human breast.
Bundy
L M
LM
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Sealy
L
L
D001940:Breast / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D051546:Cyclooxygenase 2; D004848:Epithelium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008565:Membrane Proteins; D008648:Mesoderm / Q000378:metabolism* / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics
D022782:CCAAT-Enhancer-Binding Protein-beta; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases