4.7 Article

Prostate-derived ets factor represses tumorigenesis and modulates epithelial-to-mesenchymal transition in bladder carcinoma cells

Journal

CANCER LETTERS
Volume 375, Issue 1, Pages 142-151

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2016.02.056

Keywords

Bladder; PDEF; MASPIN; NDRG family genes; Invasion; Tumorigenesis

Categories

Funding

  1. Chang Gung Memorial Hospital [CMRP-D1F0141, -D3E0042, D1D0202, -G3B1892, G2F0251, -G3E0152]
  2. Taiwan Ministry of Science and Technology [MOST 104-2314-B-182A-140-MY3, 102-2320-B-182-003-MY3]

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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 epithelialmesenchymal-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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

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