A Role for CCAAT/Enhancer Binding Protein β-Liver-enriched Inhibitory Protein in Mammary Epithelial Cell Proliferation

摘要: The transcription factor, CCAAT/enhancer binding protein beta (C/EBPbeta), regulates the expression of genes involved in proliferation and terminal differentiation. Dimerization dominant-negative C/EBPbeta-liver-enriched inhibitory (LIP) isoform with activating (LAP) inhibits transcriptional activation Consequently, an increase LIP levels may inhibit differentiation lead to proliferation. C/EBPbeta-LIP LAP are crucial for mammary gland development (G. W. Robinson et al., Genes Dev., 12: 1907-1916, 1998; T. N. Seagroves 1917-1928, 1998) also overexpressed breast cancer (B. Raught Cancer Res., 56: 4382-4386. 1996; C. A. Zahnow J. Natl. Inst., 89: 1887-1891, 1997); however, little is known about how these isoforms differentially regulate cell cycle progression. To address this question, was both glands transgenic mice cultured TM3 epithelial cells. Here we report that involuted from overexpressing contain focal diffuse alveolar hyperplasia and, less frequently, intraepithelial neoplasias (high grade) invasive noninvasive carcinomas. Likewise, cells, stably expressing C/EBPbeta-LIP, showed foci formation attributable a reentry into S-phase during cellular confluence. These results demonstrate can induce hyperplasias suggest C/EBPbeta-LIP-initiated growth cascade be susceptible additional oncogenic hits, which could result initiation progression neoplasia.