Using a multistep human urothelial model, we previously showed that green tea extract (GTE) selectively modulates actin remodeling in transformed cells (MC-T11), which resulted in increased cell adhesion and reduced cell motility (Lu et al., Clin Cancer Res 2005;11:1675-83). This study further analyzed which actin binding proteins (ABPs) might be involved in this process. Proteomic profiles of GTE treated and untreated MC-T11 cells using twodimensional gel electrophoresis coupled with liquid chromatography tandem mass spectrometry (LC/MS/MS) and matrix-assisted laser desorption and ionization time-of-flight (MALDI-TOF) identified 20 GTE-induced proteins. Among them, 3 were ABPs (tropomodulin, cofilin and annexin-I), and only annexin-I showed a dose-and time-dependent expression. The increased annexin-I correlated with actin remodeling, and was the result of transcription level up-regulation, as determined by RT-PCR, pull-down immunoblot and siRNA analyses. 5-Azacytidine, a DNA methylation inhibitor, exhibited no effect on annexin-I expression when used alone, but had an additive effect for GTE-induced annexin-I expression. Immunohistochemistry of bladder cancer tissue array showed a decrease of annexin-I expression in carcinoma in situ and low grade papillary carcinoma (n 5 32, 0% positive) compared to nontumor urothelium (n 5 18, 89% positive) (p < 0.001 by Fisher exact test), but increased in some (6 of 15, 40%) highgrade tumors. Together, GTE induced annexin-I expression plays a role in regulating actin remodeling and decreased annexin-I expression is a common event in early stage of bladder cancer development. ' 2006 Wiley-Liss, Inc.Key words: proteomics; green tea extract; annexin-I; actin remodeling; bladder cancer; chemoprevention Cancer chemoprevention is an important strategy for cancer control, and one of the key components of chemoprevention trial is to develop surrogate end point markers that can be used to determine a subject's risk of developing disease, to identify which patients might be benefited from the particular therapy, and to monitor the effectiveness of the therapy.1 Green tea, one of the most widely used beverages around the world, has shown promising anticancer effects on various cancers including bladder cancer.2-6 At the laboratory level, green tea extract (GTE) and some of its major catechin components such as epigallocatechin-3-gallate (EGCG) can produce a broad range of biological activities in various cell models, including antiproliferation, antioxidation, antiangiogenesis, apoptosis induction and the inhibition of DNA methyltransferase. 7,8 Whereas GTE based chemoprevention trials are currently ongoing for a number of human cancers including cancers of bladder and breast, there is no specific surrogate markers identified for these trials.Using a unique in vitro multistep human urothelial carcinogenic model (HUC), we recently demonstrated that GTE induces actin remodeling. 9 The HUC model we used consists of 2 cell lines derived from the same normal human urothelial clone, whic...
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