Class I histone deacetylases 1, 2 and 3 are highly expressed in renal cell cancer.
Class I histone deacetylases 1, 2 and 3 are highly expressed in renal cell cancer.
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DOI：
10.1186/1471-2407-8-381
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发表时间：
2008-12-19
期刊：
影响因子：
3.8
通讯作者：
Kristiansen G
中科院分区：
文献类型：
--
作者：
Fritzsche FR;Weichert W;Röske A;Gekeler V;Beckers T;Stephan C;Jung K;Scholman K;Denkert C;Dietel M;Kristiansen G
组蛋白去乙酰化酶（HDAC）活性增强与各种实体瘤中更具侵袭性的肿瘤行为和肿瘤进展相关。这些蛋白的过度表达及其在恶性肿瘤中的已知功能导致HDAC抑制剂（HDI）作为新的抗肿瘤药物的发展。然而，关于HDAC在肾细胞癌中的表达知之甚少。我们研究了HDAC 1，2和3的表达在106肾细胞癌和相应的正常肾组织的组织芯片上的免疫组织化学和相关的表达数据与临床病理参数，包括患者生存。几乎60%的肾细胞癌表达HDAC亚型1和2。相比之下，HDAC 3仅在所有肾肿瘤的13%中检测到，在透明细胞亚型中的表达率特别低。HDAC 3在pT 1/2肿瘤中的表达显著高于pT 3/4肿瘤。I类HDAC亚型的表达彼此相关，并与肿瘤的增殖活性相关。我们没有发现任何HDAC亚型的表达在这个肿瘤实体的预后价值。I类HDAC同种型1和2在肾细胞癌中高度表达，而HDAC 3显示低的组织学依赖性表达率。这些意想不到的表达模式差异表明I类HDAC在肾细胞癌中的替代调节机制，在计划进行同种型选择性HDI试验时应考虑到这一点。HDAC在肾癌中的表达是否能预测HDI的反应性，还有待于进一步的研究。
Enhanced activity of histone deacetylases (HDAC) is associated with more aggressive tumour behaviour and tumour progression in various solid tumours. The over-expression of these proteins and their known functions in malignant neoplasms has led to the development of HDAC inhibitors (HDI) as new anti-neoplastic drugs. However, little is known about HDAC expression in renal cell cancer. We investigated the expression of HDAC 1, 2 and 3 in 106 renal cell carcinomas and corresponding normal renal tissue by immunohistochemistry on tissue micro arrays and correlated expression data with clinico-pathological parameters including patient survival. Almost 60% of renal cell carcinomas expressed the HDAC isoforms 1 and 2. In contrast, HDAC 3 was only detected in 13% of all renal tumours, with particular low expression rates in the clear cell subtype. HDAC 3 was significantly higher expressed in pT1/2 tumours in comparison to pT3/4 tumours. Expression of class I HDAC isoforms correlated with each other and with the proliferative activity of the tumours. We found no prognostic value of the expression of any of the HDAC isoforms in this tumour entity. Class I HDAC isoforms 1 and 2 are highly expressed in renal cell cancer, while HDAC 3 shows low, histology dependent expression rates. These unexpected differences in the expression patterns suggests alternative regulatory mechanisms of class I HDACs in renal cell cancer and should be taken into account when trials with isoform selective HDI are being planned. Whether HDAC expression in renal cancers is predictive of responsiveness for HDI will have to be tested in further studies.
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影响因子：
37.3
作者：
Chavez-Blanco A;Segura-Pacheco B;Perez-Cardenas E;Taja-Chayeb L;Cetina L;Candelaria M;Cantu D;Gonzalez-Fierro A;Garcia-Lopez P;Zambrano P;Perez-Plasencia C;Cabrera G;Trejo-Becerril C;Angeles E;Duenas-Gonzalez A
通讯作者：
Duenas-Gonzalez A
影响因子：
11.5
作者：
Kato, Yukihiko;Yoshimura, Kiyoshi;Pili, Roberto
通讯作者：
Pili, Roberto
影响因子：
2.8
作者：
Halkidou, K;Gaughan, L;Robson, CN
通讯作者：
Robson, CN
组蛋白脱乙酰基酶1、2和3在前列腺癌中高度表达，而HDAC2表达与前列腺癌后psa的PSA复发时间较短有关。
影响因子：
8.8
作者：
Weichert, W.;Roeske, A.;Gekeler, V.;Beckers, T.;Stephan, C.;Jung, K.;Fritzsche, F. R.;Niesporek, S.;Denkert, C.;Dietel, M.;Kristiansen, G.
通讯作者：
Kristiansen, G.
影响因子：
3.4
作者：
Ishihama, Katsuyoshi;Yamakawa, Mitsunori;Kimura, Wataru
通讯作者：
Kimura, Wataru