Characterization of C/EBPβ isoforms in normal versus neoplastic mammary epithelial cells

A member of the CCAAT Enhancer Binding Proteins (C/EBPs) family of transcription factors, C/EBP beta, has recently proven to be an important player in both growth and differentiation of the epithelial cells in the mammary gland. When the gene for C/EBP beta is disrupted in mice, these mice fail to either develop normal mammary ducts during puberty or pregnancy, or to lactate upon parturition. C/EBP beta can be present in cells in three isoforms: C/EBP beta -1, -2, and -3. These isoforms have the same carboxy terminus but different N-termini due to alternative translational initiation at three different initiator codons within the C/EBP beta mRNA. Using a commercially available antibody specific to the C-terminus of C/EBP beta and a novel antibody specific to the N-terminus of C/EBP beta -1, we have uncovered a striking difference in the forms of C/EBP beta present in normal mammary epithelial cells versus breast cancer cell lines. C/EBP beta- 1 is found exclusively in normal mammary epithelial cells, whereas C/EBP beta- 2 is found only in dividing cells, both normal and neoplastic. Our preliminary data suggest that the prevalent form of C/EBP beta in cancer cells, C/EBP beta- 2, can activate genes which push the cell to divide, Such as cyclin D1. J. Cell. Physiol. 189: 91-105, 2001. (C) 2001 Wiley-Liss, Inc.