The expression of HDAC and its function in endometrial cancer

HDAC在子宫内膜癌中的表达及其功能

• 批准号: 22791525
• 负责人: SUZUKI Akihisa
• 金额: $ 2.08万
• 依托单位: Shinshu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22791525/
• 关键词: 子宮内膜癌; HDAC; 発現解析; 予後解析; 子宮内癌; 子官内膜癌

Over expression of histone deacetylases(HDACs) has been reported in various human malignancies, however, the expression of HDACs in endometrial tissue has not been fully understood. We examined the expression of HDAC1, HDAC2, and HDAC3 in normal and malignant endometrial tissues, and found that both HDACs were significantly up-regulated in endometrial cancer. In addition, the expression of HDAC2 was significantly increased in higher grade carcinomas and was correlated positively with the poor patient prognosis. The treatment of two HDAC inhibitors[ Trichostatin A(TSA), Apicidine(AP), and SAHA] decreased the cellular proliferation of all endometrial carcinoma cell lines examined via the up-regulation of p21 and down-regulations of cyclin A. Furthermore, the silencing of cyclin A conferred the anti-tumor activity of HDAC inhibitor. Therefore, increased HDAC2 expression is involved in the proliferation and aggressive behaviors of endometrial carcinoma, suggesting the possibility of HDAC inhibitor being a promising anti-cancer drug for endometrial carcinoma.

据报道，组蛋白脱乙酰酶（HDAC）在多种人类恶性肿瘤中过度表达，然而，HDAC在子宫内膜组织中的表达尚未完全了解。我们检测了正常和恶性子宫内膜组织中 HDAC1、HDAC2 和 HDAC3 的表达，发现这两种 HDAC 在子宫内膜癌中均显着上调。此外，HDAC2的表达在较高级别的癌症中显着增加，并且与患者不良预后呈正相关。两种 HDAC 抑制剂 [曲古抑菌素 A(TSA)、Apicidine(AP) 和 SAHA] 的治疗通过 p21 的上调和细胞周期蛋白 A 的下调来降低所有子宫内膜癌细胞系的细胞增殖。细胞周期蛋白 A 的沉默赋予了 HDAC 抑制剂的抗肿瘤活性。因此，HDAC2表达增加与子宫内膜癌的增殖和侵袭行为有关，提示HDAC抑制剂可能成为子宫内膜癌有前景的抗癌药物。

项目成果

Immunohistochemical detection of histone deacetylases in endometrial carcinoma : involvement of histon deacetylase 2 in the proliferation of endometrial carcinoma cells.

子宫内膜癌中组蛋白脱乙酰酶的免疫组织化学检测：组蛋白脱乙酰酶2参与子宫内膜癌细胞的增殖。

• 发表时间: 2010
• 期刊: Hum Pathol
• 影响因子: 3.3
• 作者: Fakhry H;Miyamoto T;Kashima H;Suzuki A;Ke H;Konishi I;Shiozawa T
• 通讯作者: Shiozawa T