Ye Lei, Li Xiaoying, Kong Xiangyin, Wang Weiqing, Bi Yufang, Hu Landian, Cui Bin, Li Xi, Ning Guang
Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Second Medical University, 197 Ruijin Er Lu, Shanghai 200025, People's Republic of China.
J Endocrinol. 2005 May;185(2):337-43. doi: 10.1677/joe.1.05963.
The ectopic ACTH syndrome is caused by abnormal expression of the POMC gene product arising from non-pituitary tumors in response to the ectopic activation of the pituitary-specific promoter of this gene. It has been proved that methylation of the CpG island in the promoter region is associated with silencing of some genes. Using bisulphite sequencing, we identified hypermethylation in the 5' promoter region of the POMC gene in three normal thymuses and one large cell lung cancer, and hypomethylation in five thymic carcinoid tumors resected from patients with ectopic ACTH syndrome. The region undergoing hypermethylation was narrowed to coordinates -417 to -260 of the POMC promoter. Furthermore, we observed that the levels of POMC expression correlated with the methylation density at -417 to -260 bp across the E2 transcription factor binding region of the POMC promoter. It is concluded that hypomethylation of the POMC promoter in thymic carcinoids correlates with POMC overexpression and the ectopic ACTH syndrome.
异位促肾上腺皮质激素（ACTH）综合征是由垂体特异性启动子的异位激活，导致非垂体肿瘤中阿片促黑皮质素原（POMC）基因产物异常表达引起的。已证实启动子区域CpG岛的甲基化与某些基因的沉默有关。我们采用亚硫酸氢盐测序法，在三个正常胸腺组织和一个大细胞肺癌中，发现POMC基因5'启动子区域存在高甲基化；而在从异位ACTH综合征患者切除的五个胸腺类癌肿瘤中，发现该区域存在低甲基化。发生高甲基化的区域被缩小至POMC启动子的-417至-260位坐标。此外，我们观察到POMC的表达水平与POMC启动子E2转录因子结合区域内-417至-260 bp处的甲基化密度相关。由此得出结论，胸腺类癌中POMC启动子的低甲基化与POMC的过表达及异位ACTH综合征相关。
