Class I histone deacetylase expression in the human cyclic endometrium and endometrial adenocarcinomas
Class I histone deacetylase expression in the human cyclic endometrium and endometrial adenocarcinomas
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DOI：
10.1093/humrep/dem241
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发表时间：
2007-11-01
影响因子：
6.1
通讯作者：
Alfer, Joachim
中科院分区：
文献类型：
--
作者：
Krusche, Claudia A.;Vloet, Anne J.;Alfer, Joachim
背景：I类组蛋白去乙酰化酶（hdac）和乙酰化酶（HATs）是由类固醇激素受体组装的转录起始前复合物的成员。最近，HDAC抑制剂被证明可以促进子宫内膜成纤维细胞和子宫内膜腺癌的分化。然而，关于HDAC和HAT在人类子宫内膜中的表达只有很少的信息。方法：采用实时或半定量RT-PCR检测绝经前子宫切除术妇女组织中HDAC-1、-2、-3和HAT (PCAF和GCN5) mRNA的表达。Western Blot和免疫组织化学检测HDAC蛋白表达。在子宫内膜腺癌（n = 17）中，用免疫组织化学方法研究了HDAC-1的表达。结果：在人子宫内膜中，HDAC-1、-2、-3和PCAF mRNA的表达无周期性变化。Western blot分析显示，HDAC-2蛋白表达在分泌期略有升高，但在分泌期显著升高（与第5-8天相比P < 0.01），而HDAC-1和hdac -3蛋白在整个月经周期均有表达。通过免疫组化，检测到HDAC蛋白在所有子宫内膜细胞类型中的核表达。在HDAC-3组，子宫内膜表面上皮免疫染色在第6-10天显著降低（与第15-18天和第24-28天相比，P < 0.01）。与正常子宫内膜相比，高比例的子宫内膜腺癌在上皮和间质室中显示HDAC-1蛋白表达受损。结论：I类HDAC和HATs在整个月经周期中都在人子宫内膜中表达，提示循环子宫内膜可能是HDAC抑制剂的潜在靶点。我们假设HDAC和/或HAT表达的改变可能与子宫内膜分化受损有关。
BACKGROUND: Class I histone deacetylases (HDACs) and acetylases (HATs) are members of transcriptional pre-initiation complexes assembled by steroid hormone receptors. Recently, HDAC inhibitors were shown to enhance differentiation of endometrial fibroblasts and endometrial adenocarcinomas. However, there is only rare information on HDAC and HAT expression in the human endometrium. METHODS: HDAC-1, -2, -3 and HAT (PCAF and GCN5) mRNA expression was studied in tissue from premenopausal women undergoing hysterectomy by real-time or serniquantitative RT-PCR. HDAC protein expression was assessed by Western Blot and immunohistochemistry. In endometrial adenocarcinomas (n = 17), HDAC-1 expression was studied by immunohistochemistry. RESULTS: In the human endometrium, HDAC-1, -2, -3 and PCAF mRNA are expressed without cyclical changes. Western blot analysis demonstrated that HDAC-2 protein expression was slightly, but significantly elevated in the secretory phase (P < 0.01 versus day 5-8), whereas HDAC-1 and -3 protein expression was constitutive throughout the menstrual cycle. By immunohistochemistry, nuclear expression of HDAC proteins was detected in all endometrial cell types. In the case of HDAC-3, immunostaining was significantly reduced in the endometrial surface epithelium on day 6-10 (P < 0.01 versus days 15-18 and 24-28). Compared to normal endometrium, a high proportion of endometrial adenocarcinomas showed impaired HDAC-1 protein expression in the epithelial and stromal compartment. CONCLUSIONS: Class I HDACs and HATs are expressed in the human endometrium throughout the menstrual cycle, suggesting the cyclic endometrium as a potential target for HDAC inhibitors. We hypothesis that alterations of HDAC and/or HAT expression are potentially involved in impaired endometrial differentiation.