Objective: Histone deacetylases (HDACs) play an important role in chromatin remodeling, gene repression and regulating cell cycle progression and differentiation. This study was designed to clarify the role of HDAC1 expression in hepatocellular carcinoma (HCC). Method: The expression of HDAC1 in 47 patients with surgically resected HCC was immunohistochemically examined and analyzed in relation to their clinicopathological factors. The patients were divided into two groups according to the expression status of HDAC1: a high HDAC1 group (n = 25) with more than 20% of positively stained cells and a low HDAC1 group (n = 22) with 20% or fewer positively stained cells. Results: A high HDAC1 expression indicated a higher incidence of cancer cell invasion into the portal vein, a poorer histological differentiation, and a more advanced TNM stage. The survival rates after a surgical resection in low and high HDAC1 patients at 1, 3, 5 and 10 years were 100, 95.5, 81.8 and 60.8% and 88.0, 60.0, 40.0 and 32.0%, respectively (p = 0.008). A multivariate analysis using the Cox regression analysis showed that a high HDAC1 expression was an independent prognostic factor of HCC in patients after hepatic resection (relative risk: 10.1, p = 0.0018). Conclusions: High HDAC1 expression might have an important role in the aggressiveness and cell dedifferentiation, and its expression status may be a useful biomarker for predicting the outcome of the patients with HCC.

Yoo CB, Jones PA: Epigenetic therapy of cancer: past, present and future. Nat Rev Drug Discov 2006;5:37–50.
Fraga MF, Ballestar E, Villar-Garea A, Boix-Chornet M, Espada J, Schotta G, Bonaldi T, Haydon C, Ropero S, Petrie K, Iyer NG, Pérez-Rosado A, Calvo E, Lopez JA, Cano A, Calasanz MJ, Colomer D, Piris MÁ, Ahn N, Mhof A, Caldas C, Jenuwein T, Esteller M: Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet 2005;37:391–400.
Kurdistani SK, Travazoiem S, Grunstein M: Mapping global histone acetylation patterns to gene expression. Cell 2004;117:721–733.
Zhang Y, LeRoy G, Seeling HP, Lane WS, Reinberg D: The dermatomyositis specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities. Cell 1998;95:279–289.
Zhang Y, Ng HH, Bromage EB, Tempst P, Bird A, Reinberg D: Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. Genes Dev 1999;13:1924–1935.
McKinsey TA, Zhang CL, Lu J, Olson EN: Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation. Nature 2000;408:106–111.
Lu J, McKinsey TA, Zhang CL, Olson EN: Regulation of skeletal myogenesis by association of the MEF2 transcription factor with class II histone deacetylases. Mol Cell 2000;6:233–244.
Doetzlhofer A, Rotheneder H, Lagger G, Koranda M, Kurtev V, Brosch G, Wintersberger E, Seiser C: Histone deacetylase 1 can repress transcription by binding to Sp1. Mol Cell Biol 1999;19:5504–5511.
Drummond DC, Noble CO, Kirpotin DB, Guo Z, Scott GK, Benz CC: Clinical development of histone deacetylase inhibitors as anticancer agents. Annu Rev Pharmacol Toxicol 2005;45:495–528.
Marks PA, Jiang X: Histone deacetylase inhibitors in programmed cell death and cancer therapy. Cell Cycle 2005;4:549–555.
Archer SY, Meng S, Shei A, Hodin RA: p21(WAF1) is required for butyrate-mediated growth inhibition of human colon cancer cells. Proc Natl Acad Sci USA 1998;95:6791–6796.
Sowa Y, Orita T, Hiranabe SM, Mizuno T, Nomura H, Sakai T: Sp3, but not Sp1, mediates the transcriptional activation of the p21/WAF1/Cip1 gene promoter by histone deacetylase inhibitor. Cancer Res 1999;59:4266–4270.
Yamashita Y, Shimada M, Harimoto N, Rikimaru T, Shirabe K, Tanaka S, Sugimachi K: Histone deacetylase inhibitor trichostatin A induces cell-cycle arrest/apoptosis and hepatocyte differentiation in human hepatoma cells. Int J Cancer 2003;103:572–576.
Insinga A, Monestiroli S, Ronzoni S, Gelmetti V, Marchesi F, Viale A, Altucci L, Nervi C, Minucci S, Pelicci PG: Inhibitors of histone deacetylases induce tumor-selective apoptosis through activation of the death receptor pathway. Nat Med 2005;11:71–76.
Guesdon JL, Ternynck AS: The use of avidin-biotin interaction in immunoenzymatic techniques. J Histochem Cytochem 1979;27:1131–1139.
Senese S, Zaragoza K, Minardi S, Muradore I, Ronzoni S, Passafaro A, Bernard L, Draetta GF, Alcalay M, Seiser C, Chiocca S: A role for histone deacetylase 1 in human tumor cell proliferation. Mol Cell Biol 2007;27:4784–4795. DOI: 10.1128/MCB.00494-07.
Whetstine JR, Ceron J, Ladd B, Dufourcq P, Reinke V, Shi Y: Regulation of tissue-specific and extracellular matrix-related genes by a class I histone deacetylase. Mol Cell 2005;18:483–490.
Huang L: Targeting histone deacetylase for the treatment of cancer and inflammatory diseases. J Cell Physiol 2006;209:611–616.
Venturelli S, Armeanu S, Pathil A, Hsieh CJ, Weiss TS, Vonthein R, Wehrmann M, Gregor M, Lauer UM, Bitzer M: Epigenetic combination therapy as a tumor-selective treatment approach for hepatocellular carcinoma. Cancer 2007;109:2132–2141.
Lai JP, Yu C, Moser CD, Aderca I, Han T, Garvey TD, Murphy LM, Garrity-Park MM, Shridhar V, Adjei AA, Roberts LR: SULF1 inhibits tumor growth and potentiates the effects of histone deacetylase inhibitors in hepatocellular carcinoma. Gastroenterology 2006;130:2130–2144.
Yang WM, Yao YL, Sun JM, Davie JR, Seto E: Isolation and characterization of cDNAs corresponding to an additional member of the human histone deacetylase gene family. J Biol Chem 1997;272:28001–28007.
Kim JH, Choi YK, Kwon HJ, Yang HK, Choi JH, Kim DY: Downregulation of gelsolin and retinoic acid receptor beta expression in gastric cancer tissues through histone deacetylase 1. J Gastroenterol Hepatol 2004;19:218–224.
Choi JH, Kwon HJ, Yoon BI, Kim JH, Han SU, Joo HJ, Kim DY: Expression profile of histone deacetylase 1 in gastric cancer tissues. Jpn J Cancer Res 2001;92:1300–1304.
Bartl S, Taplick J, Lagger G, Khier H, Kuchler K, Seiser C: Identification of mouse histone deacetylase 1 as a growth factor-inducible gene. Mol Cell Biol 1997;17:5033–5043.
Schuettengruber B, Simboeck E, Khier H, Seiser C: Autoregulation of mouse histone deacetylase 1 expression. Mol Cell Biol 2003;23:6993–7004.
Solari F, Bateman A, Ahringer J: The Caenorhabditis elegans genes egl-27 and egr-1 are similar to MTA1, a member of a chromatin regulatory complex, and are redundantly required for embryonic patterning. Development 1999;126:2483–2494.
Toh Y, Pencil SD, Nicolson GL: A novel candidate metastasis-associated gene, mta1, differentially expressed in highly metastatic mammary adenocarcinoma cell lines. J Biol Chem 1994;269:22958–22963.
Toh Y, Oki E, Oda S, Tokunaga E, Ohno S, Maehara Y, Nicolson GL, Sugimachi K: Overexpression of the MTA1 gene in gastrointestinal carcinomas: correlation with invasion and metastasis. Int J Cancer 1997;74:459–463.
Toh Y, Kuwano H, Mori M, Nicolson GL, Sugimachi K: Overexpression of metastasis-associated MTA1 mRNA in invasive oesophageal carcinomas. Br J Cancer 1999;79:1723–1726.
Hamatsu T, Rikimaru T, Yamashita Y, Aishima S, Tanaka S, Shirabe K, Shimada M, Toh Y, Sugimachi K: The role of MTA1 gene expression in human hepatocellular carcinoma. Oncol Rep 2003;10:599–604.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.