Accession Number:

ADA395516

Title:

Role of TGR-B1-Mediated Down Regulation of NF-kB/Rel Activity During Growth Arrest of Breast Cancer Cells

Descriptive Note:

Annual summary rept. 1 May 2000-30 Apr 2001

Corporate Author:

BOSTON UNIV MA

Personal Author(s):

• Guo, Shangqin
• Sonenshein, Gail

Report Date:

2001-05-01

Pagination or Media Count:

39.0

Abstract:

The NF-Kappa BRel family of dimeric transcription factors has been shown to promote cell survival, and increasing evidence suggests involvement in carcinogenesis. Recently, NF-Kappa BRel was found to be constitutively active in the nuclei of human breast cancer cell lines, as well as in 7,12-dimethylbenzaanthracene 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 BRel in the pathogenesis of the mammary gland. Furthermore, our laboratory demonstrated activation of NF-Kappa B is induced upon over-expression of Her-2neu.

Descriptors:

• *BREAST CANCER
• EPITHELIUM
• NEOPLASMS
• CARCINOGENS
• CELLS(BIOLOGY)
• PATHOGENESIS
• NUCLEI
• MAMMARY GLANDS
• GROWTH(PHYSIOLOGY)
• ONCOGENESIS

Subject Categories:

• Anatomy and Physiology
• Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE