Kenji Oyama1,2, Keita Kanki2,3, Hiroki Shimizu2, Yohei Kono2, Junya Azumi2, Kan Toriguchi4, Etsuro Hatano4, Goshi Shiota2. 1. Tottori University Hospital Cancer Center, Tottori University, Yonago, Japan. 2. Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Yonago, Japan. 3. Department of Biomedical Engineering, Faculty of Engineering, Okayama University of Science, Okayama, Japan. 4. Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Abstract
BACKGROUND: Retinoids, vitamin A and its derivatives, have an antitumor effect on hepatocellular carcinoma (HCC). The function of retinoids is exerted by the complex of retinoic acid (RA) with the heterodimer of retinoid X receptor and the RA receptor. The preferentially expressed antigen of melanoma (PRAME) acts as a dominant repressor of RA signaling by binding to the complex. The significance of PRAME on the prognosis of HCC remains to be clarified. METHODS: PRAME mRNA expression was examined by quantitative real-time polymerase chain reaction in both tumor and non-tumor tissues of 100 HCC patients who received surgical resection. The effect of PRAME knockdown on DR5-mediated RA transcriptional activity was examined. RESULTS: In tumor tissues, there were significant associations among PRAME expression, clinical stage, tumor markers, and tumor numbers. In non-tumor tissues, there were significant associations among PRAME expression, overall survival, and disease-free survival. The knockdown of PRAME caused no reduction in DR5-mediated transcriptional activity of RA, suggesting that PRAME acts via other mechanisms than the DR5 RA-responsive elements. CONCLUSION: Our findings indicate that PRAME expression is a novel prognostic marker in HCC patients.
BACKGROUND:Retinoids, vitamin A and its derivatives, have an antitumor effect on hepatocellular carcinoma (HCC). The function of retinoids is exerted by the complex of retinoic acid (RA) with the heterodimer of retinoid X receptor and the RA receptor. The preferentially expressed antigen of melanoma (PRAME) acts as a dominant repressor of RA signaling by binding to the complex. The significance of PRAME on the prognosis of HCC remains to be clarified. METHODS:PRAME mRNA expression was examined by quantitative real-time polymerase chain reaction in both tumor and non-tumor tissues of 100 HCC patients who received surgical resection. The effect of PRAME knockdown on DR5-mediated RA transcriptional activity was examined. RESULTS: In tumor tissues, there were significant associations among PRAME expression, clinical stage, tumor markers, and tumor numbers. In non-tumor tissues, there were significant associations among PRAME expression, overall survival, and disease-free survival. The knockdown of PRAME caused no reduction in DR5-mediated transcriptional activity of RA, suggesting that PRAME acts via other mechanisms than the DR5 RA-responsive elements. CONCLUSION: Our findings indicate that PRAME expression is a novel prognostic marker in HCC patients.
Authors: M Takata; N Yamanaka; T Tanaka; J Yamanaka; S Maeda; E Okamoto; H Yasojima; K Uematsu; H Watanabe; Y Uragari Journal: Jpn J Clin Oncol Date: 2000-02 Impact factor: 3.019
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