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• W2014293873 abstract "No AccessJournal of UrologyInvestigative Urology1 Sep 2008Decreased Acetylation of Histone H3 in Renal Cell Carcinoma: A Potential Target of Histone Deacetylase Inhibitorsis companion ofvon Hippel-Lindau Gene Status and Response to Vascular Endothelial Growth Factor Targeted Therapy for Metastatic Clear Cell Renal Cell CarcinomaA Phase II Trial of Gemcitabine Plus Capecitabine for Metastatic Renal Cell Cancer Previously Treated With Immunotherapy and Targeted AgentsRisk Score and Metastasectomy Independently Impact Prognosis of Patients With Recurrent Renal Cell Carcinoma Kent Kanao, Shuji Mikami, Ryuichi Mizuno, Toshiaki Shinojima, Masaru Murai, and Mototsugu Oya Kent KanaoKent Kanao More articles by this author , Shuji MikamiShuji Mikami More articles by this author , Ryuichi MizunoRyuichi Mizuno More articles by this author , Toshiaki ShinojimaToshiaki Shinojima More articles by this author , Masaru MuraiMasaru Murai More articles by this author , and Mototsugu OyaMototsugu Oya More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2008.04.136AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Recent studies suggest that alterations in chromatin structure by histone acetylation may have an important role in the neoplastic process. We evaluated histone H3 acetylation in renal cell carcinoma and the effects of a histone deacetylase inhibitor on renal cancer cell lines. Materials and Methods: The expression of acetylated histone H3 (Lys9) in renal cell carcinoma and corresponding nonneoplastic tissue specimens was evaluated. We next assessed immunohistologically the relationships between acetylated histone H3 expression and clinicopathological parameters in 44 cases of renal cell carcinoma. Furthermore, we evaluated the effects of the histone deacetylase inhibitor depsipeptide on the renal cancer cell lines Caki-1, ACHN, 769P and 786O (ATCC®). Results: Acetylated histone H3 expression was decreased in 85.0% of renal cell carcinomas compared to levels in nonneoplastic tissue. Decreased expression was related to high nuclear tumor grade and advanced pathological tumor stage (p = 0.048 and 0.032, respectively). Depsipeptide inhibited cell line proliferation in a time and dose dependent manner. Depsipeptide induced apoptosis in Caki-1, ACHN and 786O, and induced G2 cell cycle arrest in 769P. Concomitantly depsipeptide increased acetylated histone H3 and p21WAF/CIP1 expression, and induced Bcl-2 phosphorylation. Conclusions: These results suggest that the decreased acetylation of histone H3 is a common alteration in a malignant phenotype of renal cell carcinoma. Increasing the amount of acetylated histone H3 might be a therapeutic option for renal cell carcinoma. References 1 : Histone acetylation in chromatin structure and transcription. Nature1997; 389: 349. Google Scholar 2 : Roles of histone acetyltransferases and deacetylases in gene regulation. Bioessays1998; 20: 615. Google Scholar 3 : Histone acetylation and control of gene expression. J Cell Sci1991; 99: 13. Google Scholar 4 : Acetylation of proteins as novel target for antitumor therapy: review article. Amino Acids2004; 26: 435. 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Clin Cancer Res2005; 11: 3558. Google Scholar 18 : Trichostatin A, an inhibitor of histone deacetylases, strongly suppresses growth of pancreatic adenocarcinoma cells. Mol Carcinog2003; 38: 59. Google Scholar 19 : Inactivation of Bcl-2 by phosphorylation. Proc Natl Acad Sci U S A1995; 92: 4507. Google Scholar 20 : Deletion of the loop region of Bcl-2 completely blocks paclitaxel-induced apoptosis. Proc Natl Acad Sci U S A1999; 96: 3775. Google Scholar Department of Urology and Division of Diagnostic Pathology (SM), Keio University School of Medicine, Tokyo, Japan© 2008 by American Urological AssociationFiguresReferencesRelatedDetailsRelated articlesJournal of Urology17 Jul 2008von Hippel-Lindau Gene Status and Response to Vascular Endothelial Growth Factor Targeted Therapy for Metastatic Clear Cell Renal Cell CarcinomaJournal of Urology17 Jul 2008A Phase II Trial of Gemcitabine Plus Capecitabine for Metastatic Renal Cell Cancer Previously Treated With Immunotherapy and Targeted AgentsJournal of Urology17 Jul 2008Risk Score and Metastasectomy Independently Impact Prognosis of Patients With Recurrent Renal Cell Carcinoma Volume 180Issue 3September 2008Page: 1131-1136 Advertisement Copyright & Permissions© 2008 by American Urological AssociationKeywordsacetylationhistoneskidneygene expressioncarcinomarenal cellAcknowledgmentsAzusa Yamanouchi and Hiroshi Nakazawa provided technical assistance. Depsipeptide was provided by Astellas Pharma, Inc.MetricsAuthor Information Kent Kanao More articles by this author Shuji Mikami More articles by this author Ryuichi Mizuno More articles by this author Toshiaki Shinojima More articles by this author Masaru Murai More articles by this author Mototsugu Oya More articles by this author Expand All Advertisement PDF downloadLoading ..." @default.
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