Green tea polyphenol epigallocatechin-3 gallate (EGCG) affects gene expression of breast cancer cells transformed by the carcinogen 7,12-dimethylbenz[a]anthracene

Since the 1980s, the incidence of late-onset breast cancer has been increasing in the United States. Known risk factors, such as genetic modifications, have been estimated to account for similar to 5 to 10% of breast cancer cases, and these tend to be early onset. Thus, exposure to and bioaccumulation of ubiquitous environmental chemicals, such as polycyclic aromatic hydrocarbons (PAHs), have been proposed to play a role in this increased incidence. Treatment of female Sprague-Dawley rats with a single dose of the PAH 7,12-dimethylbenz[a]anthracene (DMBA) induces mammary tumors in similar to 90 to 95% of test animals. We showed previously that female rats treated with DMBA and given green tea as drinking fluid displayed significantly decreased mammary tumor burden and invasiveness and a significantly increased latency to first tumor. Here we used cDNA microarray analysis to elucidate the effects of the green tea polyphenol epigallocatechin-3 gallate (EGCG) on the gene expression profile in a DMBA-transformed breast cancer cell line. RNA was isolated, in quadruplicate, from D3-1 cells treated with 60 mu g/mL EGCG for 2, 7, or 24 h and subjected to analysis. Semiquantitative RT-PCR and Northern blot analyses confirmed the changes in the expression of 12 representative genes seen in the microarray experiments. Overall, our results documented EGCG-altered expression of genes involved in nuclear and cytoplasmic transport, transformation, redox signaling, response to hypoxia, and PAHs.