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Nulliparous CCAAT/enhancer binding protein delta (C/EBP delta) knockout mice exhibit mammary gland ductal hyperlasia

  1. Author:
    Gigliotti, A. P.
    Johnson, P. F.
    Sterneck, E.
    DeWille, J. W.

  2. Author Address

    Ohio State Univ, Dept Vet Biosci, 1900 Coffey Rd, Columbus, OH 43210 USA Ohio State Univ, Dept Vet Biosci, Columbus, OH 43210 USA Ohio State Univ, Div Mol Biol & Canc Genet, Ohio State Comprehens Canc Ctr, Columbus, OH 43210 USA NCI, Mol Mech Dev Grp, Frederick, MD 21702 USA DeWille JW Ohio State Univ, Dept Vet Biosci, 1900 Coffey Rd, Columbus, OH 43210 USA
    1. Year: 2003
  2. Journal: Experimental Biology and Medicine
    1. 228
    2. 3
    3. Pages: 278-285
  4. Type of Article: Article
  1. Abstract:

    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.

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