The Role of NF-kB in Normal and Transformed Mammary Epithelium
Abstract
The Rel/NF-kB family of transcription factors has been implicated in such diverse cellular processes as proliferation, differentiation, and apoptosis. These processes occur during mammary gland morphogenesis, and we previously demonstrated that NF-kB factors are expressed and active in the mammary gland during pregnancy and involution, when the epithelium is proliferating and undergoing apoptosis, respectively. Moreover, NF-kB activity is upregulated in breast cancer derived cell lines and primary adenocarcinomas. To address the function of NF-kB activity during early post-natal morphogenesis, the development of ikba-deficient mammary epithelium in a wild-type stromal environment was examined. Removal of this major inhibitor NF-kB transcriptional activity in the mammary gland. The ikba-deficient mammary epithelium displayed disorganization and pervasive intraductal hyperplasia, with a 2 to 3 fold increase in epithelial cell number and proliferation in virgin animals. No change in the level of apoptosis in ikba-deficient mammary epithelium, relative to controls, was detected. The extracellular matrix adjacent to ikba-deficient epithelium was greatly reduced, and epithelial adherins junctions were disrupted. These data demonstrate that NF-kB positively regulates proliferation of the mammary epithelium, and suggest that NF-kB may contribute to mammary epithelial tumorigenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2000
- Accession Number
- ADA387806
Entities
People
- Dana Brantley
- Lawrence D. Kerr
Organizations
- Vanderbilt University Medical Center