CCAAT/enhancer-binding proteins (C/EBPs) are a highly conserved family of D
NA-binding proteins that regulate cell-specific growth, differentiation, an
d apoptosis. Here, we show that induction of C/EBP delta gene expression du
ring G(0) growth arrest is a general property of mammary-derived cell lines
. C/EBP delta is not induced during G(0) growth arrest in 3T3 or IEC18 cell
s. C/EBP delta induction is G(0)-specific in mouse mammary epithelial cells
; C/EBP delta gene expression is not induced by growth arrest in the G(1),
S, or G(2) phase of the cell cycle. C/EBP delta antisense-expressing cells
(AS1 cells) maintain elevated cyclin D1 and phosphorylated retinoblastoma p
rotein levels and exhibit delayed G(0) growth arrest and apoptosis in respo
nse to serum and growth factor withdrawal. Conversely, C/EBP delta-overexpr
essing cells exhibited a rapid decline in cyclin D1 and phosphorylated reti
noblastoma protein levels, a rapid increase in the cyclin-dependent kinase
inhibitor p27, and accelerated G(0) growth arrest and apoptosis in response
to serum and growth factor withdrawal. When C/EBP delta levels were rescue
d in AS1 cells by transfection with a C/EBP delta "sense" construct, normal
G(0) growth arrest and apoptosis were restored. These results demonstrate
that C/EBP delta plays a key role in the regulation of G(0) growth arrest a
nd apoptosis in mammary epithelial cells.