Role of TGR-B1-Mediated Down Regulation of NF-kB/Rel Activity During Growth Arrest of Breast Cancer Cells
Abstract
The NF-Kappa B/Rel family of dimeric transcription factors has been shown to promote cell survival, and increasing evidence suggests involvement in carcinogenesis. Recently, NF-Kappa B/Rel was found to be constitutively active in the nuclei of human breast cancer cell lines, as well as in 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors from Sprague-Dawley rats (S-D). Malignantly transformed human mammary epithelial cells (HMEC), derived by carcinogen treatment of non-tumorigenic parental MCF-10F cells displayed increased constitutive NF-Kappa B activation. In premalignant HMECs immortalized by carcinogen treatment in vitro, NF-Kappa B activity was dysregulated in quiescence. Furthermore, founder lines of transgenic mice with targeted ectopic expression of the c-Rel subunit in the mammary gland were established. Studies, which are still in progress, have indicated the appearance of breast tumors appear by an average of 19 months, thus confirming the role of NF-Kappa B/Rel in the pathogenesis of the mammary gland. Furthermore, our laboratory demonstrated activation of NF-Kappa B is induced upon over-expression of Her-2/neu.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2001
- Accession Number
- ADA395516
Entities
People
- Gail Sonenshein
- Shangqin Guo
Organizations
- Boston University