Nuclear factor-kappaB (NF-kappaB) regulates proliferation and branching in mouse mammary epithelium.

Brantley DM, Chen CL, Muraoka RS, Bushdid PB, Bradberry JL, Kittrell F, Medina D, Matrisian LM, Kerr LD, Yull FE
Mol Biol Cell. 2001 12 (5): 1445-55

PMID: 11359934 · PMCID: PMC34596 · DOI:10.1091/mbc.12.5.1445

The nuclear factor-kappaB (NF-kappaB) family of transcription factors has been shown to regulate proliferation in several cell types. Although recent studies have demonstrated aberrant expression or activity of NF-kappaB in human breast cancer cell lines and tumors, little is known regarding the precise role of NF-kappaB in normal proliferation and development of the mammary epithelium. We investigated the function of NF-kappaB during murine early postnatal mammary gland development by observing the consequences of increased NF-kappaB activity in mouse mammary epithelium lacking the gene encoding IkappaBalpha, a major inhibitor of NF-kappaB. Mammary tissue containing epithelium from inhibitor kappaBalpha (IkappaBalpha)-deficient female donors was transplanted into the gland-free mammary stroma of wild-type mice, resulting in an increase in lateral ductal branching and pervasive intraductal hyperplasia. A two- to threefold increase in epithelial cell number was observed in IkappaBalpha-deficient epithelium compared with controls. Epithelial cell proliferation was strikingly increased in IkappaBalpha-deficient epithelium, and no alteration in apoptosis was detected. The extracellular matrix adjacent to IkappaBalpha-deficient epithelium was reduced. Consistent with in vivo data, a fourfold increase in epithelial branching was also observed in purified IkappaBalpha-deficient primary epithelial cells in three-dimensional culture. These data demonstrate that NF-kappaB positively regulates mammary epithelial proliferation, branching, and functions in maintenance of normal epithelial architecture during early postnatal development.

MeSH Terms (18)

Animals Apoptosis Cell Division Cells, Cultured DNA-Binding Proteins Epithelial Cells Extracellular Matrix Female Genes, Reporter Humans I-kappa B Proteins In Situ Nick-End Labeling Mammary Glands, Animal Mice Mice, Transgenic NF-kappa B NF-KappaB Inhibitor alpha Transplants

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