Histone deacetylases 1, 2 and 3 are highly expressed in prostate cancer and HDAC2 expression is associated with shorter PSA relapse time after radical prostatectomy

被引:387
作者
Weichert, W.
Roeske, A.
Gekeler, V.
Beckers, T.
Stephan, C.
Jung, K.
Fritzsche, F. R. [1 ]
Niesporek, S.
Denkert, C.
Dietel, M.
Kristiansen, G. [1 ]
机构
[1] Univ Zurich Hosp, Inst Surg Pathol, CH-8091 Zurich, Switzerland
关键词
HDAC; prostate cancer; prognostic marker; immunohistochemistry; SUBEROYLANILIDE HYDROXAMIC ACID; HUMAN BREAST-CANCER; VALPROIC ACID; UP-REGULATION; IN-VITRO; INHIBITORS; CELLS; DIFFERENTIATION; APOPTOSIS; MIGRATION;
D O I
10.1038/sj.bjc.6604199
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
High activity of histone deacetylases (HDACs) causes epigenetic alterations associated with malignant cell behaviour. Consequently, HDAC inhibitors have entered late-phase clinical trials as new antineoplastic drugs. However, little is known about expression and function of specific HDAC isoforms in human tumours including prostate cancer. We investigated the expression of class I HDACs in 192 prostate carcinomas by immunohistochemistry and correlated our findings to clinicopathological parameters including follow-up data. Class I HDAC isoforms were strongly expressed in the majority of the cases (HDAC1: 69.8%, HDAC2: 74%, HDAC3: 94.8%). High rates of HDAC1 and HDAC2 expression were significantly associated with tumour dedifferentiation. Strong expression of all HDACs was accompanied by enhanced tumour cell proliferation. In addition, HDAC2 was an independent prognostic marker in our prostate cancer cohort. In conclusion, we showed that the known effects of HDACs on differentiation and proliferation of cancer cells observed in vitro can also be confirmed in vivo. The class I HDAC isoforms 1, 2 and 3 are differentially expressed in prostate cancer, which might be important for upcoming studies on HDAC inhibitors in this tumour entity. Also, the highly significant prognostic value of HDAC2 clearly deserves further study.
引用
收藏
页码:604 / 610
页数:7
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