Effect of Green Tea Polyphenols on Breast Cancer Signaling
Abstract
This project aimed to define the effects of green tea polyphenols (GTPs) on cell signaling pathways and on mammary tumorigenesis in MMTV/c-neu transgenic mice. The studies showed that the major polyphenol in green tea, EGCG, did not impair erbB-2 tyrosine phosphorylation or EGF-dependent activation of MAP kinase in transformed or untransformed MCFlOA cells, and that orally administered green tea or GTPs did not inhibit mammary tumorigenesis. Subsequent studies focused on the mechanism by which EGCC inhibits mammary epithelial cell cycle progression. EGCG inhibited S phase entry in epidermal growth factor (EGF)-stimulated MCFlOA breast epithelial cells when provided in GO or mid Gl, but not when provided after the late G1 restriction point. EGCG induced p21 CIP1/WAF1/SDI1 inhibited cyclin Dl-associated pRB kinase activity, increased the association of p21 with cyclin Dl, and impaired pRB phosphorylation. EGCG induced p21 expression at the mRNA level. In addition, the ability of EGCG to induce p21 depended on the addition of EGE, indicating that EGCG synergizes with growth factor-dependent signals. While these findings provide a mechanism by which polyphenolic compounds may inhibit proliferation, their relevance to breast cancer chemoprevention remains unclear due to the lack of effect of tea polyphenols on tumorigenesis in MMTV/c-neu transgenic mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2000
- Accession Number
- ADA387639
Entities
People
- David Cobrinik
Organizations
- Columbia University