| The Nuclear Factor-κB (NF-κB) family of transcription factors is aberrantly elevated in many human breast cancer tissue specimens and cell lines. NF-κB activity, which promotes growth, survival and the transformed phenotype, can be inhibited by treatment with various anti-oxidants. Green tea extracts contain several antioxidant molecules, which have anti-carcinogenic properties. Since the incidence of breast cancer is low in areas of the world with high green tea consumption, the hypothesis that green tea inhibits breast cancer was tested. Using the Sprague-Dawley model of DMBA-induced breast cancer, the effects of green tea extracts on mammary tumor formation were assessed. A 70% decrease in the total tumor burden was detected in female rats administered green tea compared to control water-fed rats. The number of invasive tumors was also significantly reduced. Human breast cancer cell lines were treated with either a green tea polyphenol (GTP) mixture or epigallocatechin 3-gallate (EGCG), the most abundant polyphenol component contained in green tea. Treatment with low doses of GTP or EGCG slowed the growth of the cells, while higher doses caused apoptotic cell death. These findings indicate that green tea inhibits breast cancer cell growth in vitro and reduces tumor burden in vivo. The effects of green tea on NF-κB activity were next assessed. EGCG treatment reduced NF-κB binding in NF639 cells, but not in Hs578T breast cancer cells. Thus, while additional work is required to elucidate the mechanism of green tea action, these results indicate that green tea extracts may be useful as an adjuvant to conventional chemotherapeutic treatments.; The hypothesis that NF-κB plays a role in the development of the normal mammary gland was addressed using a transgenic mouse model with targeted overexpression of the NF-κB/Rel inhibitory molecule, IκB-α, in the mammary glands. Specifically, three MMTV-S32/36A IκB-α transgenic mouse founder lines were identified and analyzed. Whole mount analysis revealed that IκB-α overexpression caused a delay in the development of the normal branching architecture of the gland during early pregnancy at days 5.5 and 7.5, which seemed to correct itself by late pregnancy. No effects on regression were noted. These results demonstrate NF-κB plays a role in early mammary gland development. |
