Wang Weimin, Fu Li, Li Shengli, Xu Zhiming, Li Xingang
School of Medicine, Shandong University, Jinan, 250012, China.
Department of Neurosurgery and Surgery Room, Qingdao Municipal Hospital, Qingdao, 266071, China.
Cell Biol Int. 2017 Dec;41(12):1290-1295. doi: 10.1002/cbin.10834. Epub 2017 Aug 29.
The pathogenesis of pituitary tumors (PT) is unclear. Deregulation of apoptosis is one of the factors involving tumor growth. Histone deacetylases (HDAC) have an active role in multiple cellular activities. This study aims to investigate the role of HDAC in the interference with apoptosis in PT. In this study, PT samples were collected from 20 patients after surgery. The expression of HDAC and p53 was analyzed in the PT samples. PT cell line, AtT-20 cells, was cultured to test the role of HDAC in the regulation of apoptosis in PT cells. The results showed that the high levels of HDAC11 and lower levels of p53 were detected in PT. A negative correlation was detected between the data of HDAC11 and p53. A complex of HDAC11 and HEY1, the gene transcription factor of p53, was detected in the PT cells. Less acetylated HEY1 was found in the PT cells. In addition, lower levels of HEY1 and the gene transcription activities were detected at the PT53 promoter locus. This phenomenon was mimicked by overexpression of HDAC11 in AtT-20 cells. Knockdown of HDAC11 enhanced the p53 expression in AtT-20 cells. In conclusion, HDAC11 interferes with p53 expression in PT cells. The fact suggests that inhibition of HDAC11 has therapeutic potential in the treatment of PT.
垂体瘤(PT)的发病机制尚不清楚。细胞凋亡失调是肿瘤生长的因素之一。组蛋白去乙酰化酶(HDAC)在多种细胞活动中发挥着积极作用。本研究旨在探讨HDAC在干扰垂体瘤细胞凋亡中的作用。在本研究中,收集了20例患者术后的垂体瘤样本。分析了垂体瘤样本中HDAC和p53的表达。培养垂体瘤细胞系AtT-20细胞,以测试HDAC在垂体瘤细胞凋亡调控中的作用。结果显示,在垂体瘤中检测到HDAC11水平升高和p53水平降低。HDAC11和p53的数据之间存在负相关。在垂体瘤细胞中检测到HDAC11与p53的基因转录因子HEY1形成的复合物。在垂体瘤细胞中发现乙酰化的HEY1较少。此外,在PT53启动子位点检测到较低水平的HEY1和基因转录活性。在AtT-20细胞中过表达HDAC11模拟了这种现象。敲低HDAC11可增强AtT-20细胞中p53的表达。总之,HDAC11干扰垂体瘤细胞中p53的表达。这一事实表明,抑制HDAC11在垂体瘤治疗中具有治疗潜力。