CCAAT/enhancer-binding protein-delta (C/EBP-delta) is induced in growth-arrested mouse mammary epithelial cells

CCAAT/enhancer binding proteins (C/EBPs) are a highly conserved family of DNA-binding proteins that regulate cell growth and differentiation in a highly tissue-specific manner, These experiments investigated the influence of the cell cycle on C/EBP isoform expression in mammary epithelial cells (COMMA D) and fibroblasts (NIH3T3). C/EBP-delta gene expression is induced in COMMA D cells arrested in G(0) by serum and growth factor withdrawal or contact inhibition. C/EBP-delta mRNA, nuclear protein content, and DNA binding activity increase during G(0) growth arrest and decrease after cell cycle induction in COMMA D cells. Growth arrest is markedly delayed in COMMA D cells expressing a C/EBP-delta antisense construct, C/EBP-beta is induced during G(1) of the cell cycle. In contrast to COMMA D cells, C/EBP-beta and C/EBP-delta mRNA levels remain relatively constant in growth-arrested and cell cycle induced NIH3T3 cells. However, C/EBP homologous protein (CHOP10) mRNA levels markedly increase in growth arrested NIH3T3 cells. Both COMMA D and NIH3T3 cells express growth arrest-specific (gas1) and JunD during G(0). These results demonstrate that COMMA D and NIH3T3 cells achieve a common growth arrest (G(0)) state by cell-specific strategies that involve the induction of different C/EBP isoforms.