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.

Maspin is a PTEN-Upregulated and p53-Upregulated Tumor Suppressor Gene and Acts as an HDAC1 Inhibitor in Human Bladder Cancer

“…Maspin belongs to the serine protease inhibitor/noninhibitor superfamily and has dissimilar effects according to the types of cancer [4]. Although reports concerning the biological function of maspin in bladder cancer are still contradictory, our previous studies have indicated that maspin is the downstream gene of the prostate-derived Ets factor (PDEF) and growth differentiation factor 15 (GDF15), which are antitumor genes in bladder carcinoma cells [18,19].…”

“…The culture media were replaced with RPMI-1640 medium plus 10% FCS and 5 µg/mL polybrene (Santa Cruz Biotechnology, Santa Cruz, CA, USA) and transduced with maspin shRNA Lentiviral particles (sc-35859, Santa Cruz Biotechnology). Two days after transduction, the cells were selected by incubating with 10 µg/mL puromycin dihydrochloride for at least another three generations, as described in a previous study [19]. The p53-knockdown RT-4 (RT4_shp53), PTEN-knockdown RT-4 (RT4_shPTEN) and mock-knockdown RT-4 (RT4_shCOL) cells were cloned as described previously [39].…”

Glutamate Ionotropic Receptor Kainate Type Subunit 3 (GRIK3) promotes epithelial‐mesenchymal transition in breast cancer cells by regulating SPDEF/CDH1 signaling

“…It has also been demonstrated that SPDEF acts as a tumor and metastasis suppressor in multiple epithelium‐derived cancers . For example, SPDEF inhibits survival of prostate cancer cells through the androgen receptor (AR) relevant for cancer signaling, suppresses colorectal cancer through the E‐cadherin and β‐catenin pathway, and modulates epithelial‐mesenchymal‐transition (EMT) to lower migration and invasion abilities of bladder carcinoma cells by upregulating E‐cadherin expression and downregulating the expression of N‐cadherin, SNAIL, SLUG, and vimentin . SPDEF is an important molecule for driving invasive mucinous adenocarcinoma of the lung (IMA) transformation …”

MART-10 represses cholangiocarcinoma cell growth and high vitamin D receptor expression indicates better prognosis for cholangiocarcinoma

“…Cells were transiently transfected using the X-tremeGENE HP DNA transfection reagent (Roche Diagnostics, Indianapolis, IN) with 1 μg/well of reporter vector and 0.5 μg/well of the pCMVSPORTβgal (Invitrogen). The luciferase activity was adjusted for transfection efficiency using the normalization control plasmid pCMVSPORTβgal as previously described57.…”