Immunohistochemical detection of histone deacetylases in endometrial carcinoma: involvement of histone deacetylase 2 in the proliferation of endometrial carcinoma cells
Immunohistochemical detection of histone deacetylases in endometrial carcinoma: involvement of histone deacetylase 2 in the proliferation of endometrial carcinoma cells
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DOI：
10.1016/j.humpath.2009.11.012
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发表时间：
2010-06-01
期刊：
影响因子：
3.3
通讯作者：
Shiozawa, Tanri
中科院分区：
文献类型：
--
作者：
Fakhry, Hussein;Miyamoto, Tsutomu;Shiozawa, Tanri
组蛋白去乙酰化酶的过度表达已被报道在各种人类恶性肿瘤中，然而，组蛋白去乙酰化酶在子宫内膜组织中的表达并不完全清楚。在本研究中，组蛋白去乙酰化酶1，组蛋白去乙酰化酶2和Ki-67的表达进行了检查，在30个正常和66个恶性子宫内膜组织样本。结果表示为阳性指数，并与Ki-67阳性指数和患者生存率进行比较。采用6种子宫内膜癌细胞系，研究了2种组蛋白去乙酰化酶抑制剂-阿匹西定和阿匹西定对细胞增殖和细胞周期调控因子如细胞周期蛋白（D1、E和A）、p21、p27和p16表达的影响。组蛋白去乙酰化酶I（79.8 ± 33.0，平均值± SD）和组蛋白去乙酰化酶2（106.3 ± 41.9）的阳性指数在子宫内膜癌中高于正常子宫内膜，组蛋白去乙酰化酶2有显著差异。组蛋白去乙酰化酶2的阳性指数在高级别癌中（3级阳性指数，124.9 +/- 28.4）与1级肿瘤（86.0 +/- 41.0）相比显著增加，并与Ki-67呈正相关。此外，组蛋白去乙酰化酶2阳性的癌患者与组蛋白去乙酰化酶2阴性的癌患者相比预后较差（P = 0.048）。用阿司他丁A或阿匹西定处理抑制了所有检测的细胞系的增殖，与p21表达增加和细胞周期蛋白D1和细胞周期蛋白A表达下调相关。这些结果表明，增加组蛋白去乙酰化酶2的表达参与了子宫内膜癌的侵略行为的收购，并建议组蛋白去乙酰化酶抑制剂是一个有前途的抗癌药物，这种癌。(C)2010年爱思唯尔公司All rights reserved.
Overexpression of histone deacetylases has been reported in various human malignancies; however, the expression of histone deacetylases in endometrial tissue is not fully understood. In the present study, the expression of histone deacetylase 1, histone deacetylase 2, and Ki-67 was examined immunohistochemically in 30 normal and 66 malignant endometrial tissue samples. The results were expressed as a positivity index and compared with the positivity index for Ki-67 and rates of patient survival. The effect of 2 histone deacetylase inhibitors, trichostatin A and apicidine, on cell proliferation and the expression of cell cycle regulators such as cyclins (D1, E, and A), p21, p27, and p16 were investigated using 6 endometrial carcinoma cell lines. The positivity index for histone deacetylase I (79.8 +/- 33.0, mean +/-SD) and histone deacetylase 2 (106.3 +/- 41.9) was higher in endometrial carcinoma than the normal endometrium, with a significant difference for histone deacetylase 2. The positivity index for histone deacetylase 2 was significantly increased in higher-grade carcinomas (positivity index for grade 3, 124.9 +/- 28.4) compared with grade 1 tumors (86.0 +/- 41.0) and was positively correlated with that for Ki-67. In addition, patients with histone deacetylase 2 positive carcinomas had a poor prognosis compared with those with histone deacetylase 2 negative carcinoma (P = .048). Treatment with trichostatin A or apicidine suppressed the proliferation in all cell lines examined, in association with increased expression of p21 and down-regulation of cyclin D1 and cyclin A expression. These results indicated that increased histone deacetylase 2 expression is involved in the acquisition of aggressive behavior by endometrial carcinoma and suggest histone deacetylase inhibitor to be a promising anticancer drug for this carcinoma. (C) 2010 Elsevier Inc. All rights reserved.