title: Prostate-derived ets factor represses tumorigenesis and modulates epithelial-to-mesenchymal transition in bladder carcinoma cells.
abstract: Prostate-derived Ets (E-twenty six) factor (PDEF), an epithelium-specific member of the Ets family of transcription factors, has been shown to play a role in suppressing the development of many epithelium-derived cancers such as prostate and breast cancer. It is not clear, however, whether PDEF is involved in the development or progression of bladder cancer. In a comparison between normal urothelium and bladder tumor tissue, we identified significant decreases of PDEF in the tumor tissue. Further, the immunohistochemistry assays indicated a significantly higher immunostaining of PDEF in low-grade bladder tumors. Additionally, the highly differentiated transitional-cell bladder carcinoma RT-4 cells expressed significantly more PDEF levels than the bladder carcinoma HT1376 and the T24 cells. Ectopic overexpression of PDEF attenuated proliferation, invasion, and tumorigenesis of bladder carcinoma cells in vitro and in vivo. PDEF enhanced the expression levels of mammary serine protease inhibitor (MASPIN), N-myc downstream regulated gene 1 (NDRG1), KAI1, and B-cell translocation gene 2 (BTG2). PDEF modulated epithelial-mesenchymal-transition (EMT) by upregulating E-cadherin expression and downregulating the expression of N-cadherin, SNAIL, SLUG, and vimentin, leading to lower migration and invasion abilities of bladder carcinoma cells. Filamentous actin (F-actin) polarization and remodeling were observed in PDEF-knockdown RT-4 cells. Our results suggest that PDEF gene expression is associated with the extent of bladder neoplasia and PDEF modulated the expressions of EMT-related genes. The induction of BTG2, NDRG1, MASPIN, and KAI1 gene expressions by PDEF may explain the inhibitory functions of PDEF on the proliferation, invasion, and tumorigenesis in bladder carcinoma cells.
authors.affiliation: Department of Urology, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan, Taiwan; Department of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan.
authors.forename: Ke-Hung
authors.initials: KH
authors.lastname: Tsui
authors.affiliation: Department of Urology, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan, Taiwan; Graduate Institute of Clinical Medical Science, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan.
authors.forename: Yu-Hsiang
authors.initials: YH
authors.lastname: Lin
authors.affiliation: Department of Anatomy, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan.
authors.forename: Li-Chuan
authors.initials: LC
authors.lastname: Chung
authors.affiliation: Department of Anatomy, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan.
authors.forename: Sung-Ting
authors.initials: ST
authors.lastname: Chuang
authors.affiliation: School of Nursing, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan.
authors.forename: Tsui-Hsia
authors.initials: TH
authors.lastname: Feng
authors.affiliation: Zebafish Center, General Surgery Department, Chang Gung Memorial Hospital, Keelung, Taiwan.
authors.forename: Kun-Chun
authors.initials: KC
authors.lastname: Chiang
authors.affiliation: Department of Urology, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan, Taiwan; Department of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan.
authors.forename: Phei-Lang
authors.initials: PL
authors.lastname: Chang
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan.
authors.forename: Chi-Ju
authors.initials: CJ
authors.lastname: Yeh
authors.affiliation: Department of Urology, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan, Taiwan; Department of Anatomy, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan. Electronic address: hhj143@mail.cgu.edu.tw.
authors.forename: Horng-Heng
authors.initials: HH
authors.lastname: Juang
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics / Q000378:metabolism*; D047368:Tumor Burden; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D050783:Proto-Oncogene Proteins c-ets; C403974:SPDEF protein, human
keywords: Bladder; Invasion; MASPIN; NDRG family genes; PDEF; Tumorigenesis