title: Annexin-I as a potential target for green tea extract induced actin remodeling.
abstract: 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 two-dimensional 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 = 32, 0% positive) compared to nontumor urothelium (n = 18, 89% positive) (p < 0.001 by Fisher exact test), but increased in some (6 of 15, 40%) high-grade 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.
authors.affiliation: Department of Clinic Molecular Pharmacology, Comprehensive Cancer Center at City of Hope National Medical Center, Duarte, California, USA.
authors.forename: Gui-Shan
authors.initials: GS
authors.lastname: Xiao
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Jin
authors.forename: Qing-Yi
authors.initials: QY
authors.lastname: Lu
authors.forename: Zuo-Feng
authors.initials: ZF
authors.lastname: Zhang
authors.forename: Arie
authors.initials: A
authors.lastname: Belldegrun
authors.forename: Robert
authors.initials: R
authors.lastname: Figlin
authors.forename: Allan
authors.initials: A
authors.lastname: Pantuck
authors.forename: Yun
authors.initials: Y
authors.lastname: Yen
authors.forename: Frederick
authors.initials: F
authors.lastname: Li
authors.forename: Jianyu
authors.initials: J
authors.lastname: Rao
mesh_terms: D000199:Actins / Q000378:metabolism*; D017305:Annexin A1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002278:Carcinoma in Situ / Q000378:metabolism / Q000473:pathology; D002291:Carcinoma, Papillary / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002461:Cell Line, Transformed; D015180:Electrophoresis, Gel, Two-Dimensional; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D010449:Peptide Mapping; D010936:Plant Extracts / Q000494:pharmacology*; D020543:Proteome; D034741:RNA, Small Interfering / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013662:Tea; D046888:Tissue Array Analysis; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology; D019459:Urothelium / Q000378:metabolism / Q000473:pathology
chemical_list: D000199:Actins; D017305:Annexin A1; D010936:Plant Extracts; D020543:Proteome; D034741:RNA, Small Interfering; D013662:Tea