Nulliparous CCAAT/enhancer binding proteinδ (C/EBPδ) knockout mice exhibit mammary gland ductal hyperlasia

被引:37
作者
Gigliotti, AP
Johnson, PF
Sterneck, E
DeWille, JW
机构
[1] Ohio State Univ, Dept Vet Biosci, Columbus, OH 43210 USA
[2] Ohio State Univ, Div Mol Biol & Canc Genet, Ohio State Comprehens Canc Ctr, Columbus, OH 43210 USA
[3] NCI, Mol Mech Dev Grp, Frederick, MD 21702 USA
关键词
C/EBP delta; mammary epithelial cell; involution; estrus cycle; nulliparous; EPITHELIAL-CELL PROLIFERATION; PROGESTERONE-RECEPTOR; GENE-EXPRESSION; GROWTH ARREST; ADIPOCYTE DIFFERENTIATION; ESTROUS-CYCLE; BETA; ALPHA; TRANSCRIPTION; BREAST;
D O I
10.1177/153537020322800306
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
CCAAT/Enhancer binding proteins (C/EBPs) are a family of nuclear proteins that function in the control of cell growth, death, and differentiation. We previously reported that C/EBPdelta plays a key role in mammary epithelial cell Go growth arrest. In this report, we investigated the role of C/EBPB in mammary gland development and function using female mice homozygous for a targeted deletion of C/EBPdelta (C/EBPdelta -/-). C/EBPdelta -/- females develop normally and exhibit normal reproductive and lactational performance. Adult nulliparous C/EBPdelta -/- females, however, exhibit mammary epithelial cell growth control defects. The mean number of mammary ductal branches is significantly higher in adult nulliparous C/EBP6 -/- females compared with C/EBPdelta +/+ (wild-type control) females (66.8 +/- 5.2 vs 42.9 +/- 6.3 branch points/field, P < 0.01). In addition, the mean total mammary gland cellular volume occupied by epithelium is significantly higher in adult nulliparous C/EBPdelta -/- females compared with C/EBPdelta +/+ controls (29.0 +/- 1.4 vs 20.4 +/- 1.3, P < 0.001). Our results showed that the BrdU labeling index was significantly higher in mammary epithelial cells from nulliparous C/EBPdelta -/- females compared with C/EBPdelta +/+ controls during the proestrus/estrus (4.55 +/- 0.70 vs 2.14 +/- 0.43, P < 0.01) and metestrus/diestrus (6.92 +/- 0.75 vs 3.98 +/- 0.43 P < 0.01) phases of the estrus cycle. In contrast, the percentage of mammary epithelial cells undergoing apoptosis during both phases of the estrus cycle did not differ between C/EBPdelta -/- and C/EBPdelta +/+ females. The increased epithelial cell content and proliferative capacity was restricted to the nulliparous C/EBPdelta -/- females as no differences in mammary gland morphology, ductal branching or total epithelial content were observed between multiparous C/EBPdelta -/- and C/EBPdelta +/+ females. These results demonstrate that C/EBPdelta plays a novel role in mammary epithelial cell growth control that appears to be restricted to the nulliparous mammary gland.
引用
收藏
页码:278 / 285
页数:8
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