Characterization of C/EBPbeta isoforms in normal versus neoplastic mammary epithelial cells.
A member of the CCAAT Enhancer Binding Proteins (C/EBPs) family of transcription factors, C/EBPbeta, 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/EBPbeta is disrupted in mice, these mice fail to either develop normal mammary ducts during puberty or pregnancy, or to lactate upon parturition. C/EBPbeta can be present in cells in three isoforms: C/EBPbeta-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/EBPbeta mRNA. Using a commercially available antibody specific to the C-terminus of C/EBPbeta and a novel antibody specific to the N-terminus of C/EBPbeta-1, we have uncovered a striking difference in the forms of C/EBPbeta present in normal mammary epithelial cells versus breast cancer cell lines. C/EBPbeta- 1 is found exclusively in normal mammary epithelial cells, whereas C/EBPbeta- 2 is found only in dividing cells, both normal and neoplastic. Our preliminary data suggest that the prevalent form of C/EBPbeta in cancer cells, C/EBPbeta- 2, can activate genes which push the cell to divide, such as cyclin D1.
Eaton
E M
EM
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Hanlon
M
M
Bundy
L
L
Sealy
L
L
D000906:Antibodies / Q000276:immunology; D001940:Breast / Q000166:cytology / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000276:immunology / Q000378:metabolism* / Q000502:physiology*; D002277:Carcinoma / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D014407:Tumor Cells, Cultured
D000906:Antibodies; D022782:CCAAT-Enhancer-Binding Protein-beta; D020033:Protein Isoforms; D019938:Cyclin D1