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

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Abstract
A member of the CCAAT Enhancer Binding Proteins (C/EBPs) family of transcription factors, C/EBPβ, 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/EBPβ is disrupted in mice, these mice fail to either develop normal mammary ducts during puberty or pregnancy, or to lactate upon parturition. C/EBPβ can be present in cells in three isoforms: C/EBPβ‐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/EBPβ mRNA. Using a commercially available antibody specific to the C‐terminus of C/EBPβ and a novel antibody specific to the N‐terminus of C/EBPβ‐1, we have uncovered a striking difference in the forms of C/EBPβ present in normal mammary epithelial cells versus breast cancer cell lines. C/EBPβ‐ 1 is found exclusively in normal mammary epithelial cells, whereas C/EBPβ‐ 2 is found only in dividing cells, both normal and neoplastic. Our preliminary data suggest that the prevalent form of C/EBPβ in cancer cells, C/EBPβ‐ 2, can activate genes which push the cell to divide, such as cyclin D1.