TEA EXTRACTS CONFER ITS ANTIPROLIFERATING EFFECTS THROUGH INHIBITION OF NICOTINE- AND ESTROGEN-INDUCED 9-NICOTINIC ACETYLCHOLINE RECEPTOR UPREGULATION IN HUMAN BREAST CANCER CELLS

摘要

Breast cancer is the second leading cause of cancer-related death among women in the United States. Large cohort studies performed in the U.S. and Japan have indicated that the risk of developing breast cancer is associated with active and passive smoking. Cigarette smoke is a complex mixture of over 4,000 chemical constituents and contains nicotine (Nic) as a major carcinogenic component. Studies performed using ~(14)C-Nic showed that 80 to 90% of inhaled Nic is absorbed systemically during smoking. Nic concentrations in plasma average about 15 ng/mL immediately after smoking and are extremely high in the saliva and gastric juices (>1300 and >800 ng/mL, respectively). Repeated exposure of non-cancerous human breast epithelial (MCF-10A) cells to the tobacco-specific carcinogen 4-(methylnitrosamino)-l-(3-pyridyl)-l-butanone (NNK) results in xenografted tumor formation in nude mouse models and anchorage-independent colony formation in soft agar. In vivo studies have demonstrated that Nic promotes the growth of solid tumors, suggesting that Nic might contribute to the progression of cell proliferation, invasion, and angiogenesis in tumors. These results imply that Nic alteration of normal breast epithelial cells may also contribute to breast tumorigenesis.