Hypermethylation of the p16 gene promoter in pterygia and its association with the expression of DNA methyltransferase 3b.
Hypermethylation of the p16 gene promoter in pterygia and its association with the expression of DNA methyltransferase 3b.
复制标题
翼状胬肉中 p16 基因启动子的高甲基化及其与 DNA 甲基转移酶 3b 表达的关系。
作者：
Pei;Ya‐Wen Cheng;Chun;S. Tseng;Pak Sam Chau;Y. Tsai
目的
翼状胬肉长期以来被认为是一种退行性疾病。在发现p53蛋白在上皮中异常表达后，研究人员提出翼状胬肉可能是一种肿瘤，但需要更多证据来支持这一假设。 p16 基因 (CDKN2A) 启动子的异常甲基化和由此产生的基因沉默在多种人类癌症的发病机制中发挥着重要作用。本研究的目的是研究翼状胬肉中 p16 启动子的高甲基化以及这种高甲基化与 p16 和 DNA 甲基转移酶 3b (DNMT3b) 蛋白表达之间的关系。
方法
我们分别通过甲基化特异性聚合酶链反应和免疫组织化学研究了 129 例翼状胬肉和 16 例正常结膜标本中 p16 的甲基化状态以及 p16 和 DNMT3b 蛋白的表达。对结果进行统计分析。
结果
在 129 份翼状胬肉标本中，有 21 份（16.3%）检测到 p16 基因启动子的高甲基化。其中p16蛋白表达阳性46例（35.7%），阴性83例（64.3%）。 p16 的染色仅限于上皮层的细胞核。我们观察到 p16 启动子的高甲基化与 p16 蛋白的表达之间存在显着的反向相关性 (p=0.006)。 38 例（29.5%）翼状胬肉标本的 DNMT3b 蛋白表达呈阳性，91 例（70.5%）呈阴性。 DNMT3b 染色仅限于上皮层的细胞核。 p16 启动子的高甲基化与 DNMT3b 蛋白的表达之间存在显着相关性 (p<0.001)。
结论
p16基因启动子在翼状胬肉中高甲基化，这种高甲基化与DNMT3b蛋白的阳性表达和p16蛋白的抑制密切相关。这些数据提供了分子证据，表明甲基化发生在翼状胬肉中，并且可能在翼状胬肉的发展中发挥作用。
PURPOSE
A pterygium has long been considered as a degenerative condition. After p53 protein was found to be abnormally expressed in the epithelium, researchers suggested that a pterygium may be a tumor, but additional evidence is required to support this hypothesis. Aberrant methylation of the p16 gene (CDKN2A) promoter and resultant gene silencing play important roles in the pathogenesis of many types of human cancers. The purpose of this study was to investigate hypermethylation of the p16 promoter in pterygia and the relationship between this hypermethylation and the expression of p16 and DNA methyltransferase 3b (DNMT3b) proteins.
METHODS
We studied the methylation status of p16 and the expression of p16 and DNMT3b proteins by performing methylation-specific polymerase chain reaction and immunohistochemistry, respectively, in specimens of 129 pterygia and 16 normal conjunctiva. The results were statistically analyzed.
RESULTS
Hypermethylation of the p16 gene promoter was detected in 21 (16.3%) of 129 pterygial specimens. Among them, 46 (35.7%) were positive for p16 protein expression, and 83 (64.3%) were negative. Staining for p16 was limited to the nuclei of the epithelial layer. We observed a significant reverse correlation between hypermethylation of the p16 promoter and the expression of p16 protein (p=0.006). Thirty-eight (29.5%) pterygial specimens were positive for DNMT3b protein expression, and 91 (70.5%) were negative. DNMT3b staining was limited to the nuclei of the epithelial layer. A significant correlation was found between hypermethylation of the p16 promoter and the expression of DNMT3b protein (p<0.001).
CONCLUSIONS
The p16 gene promoter was hypermethylated in pterygia, and this hypermethylation was strongly linked to expression of the positive expression of DNMT3b protein and to the suppression of p16 protein. These data provided molecular evidence that methylation occurs in pterygia and that it may play a role in the their development.
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影响因子：
11.2
作者：
J. Issa;S. Baylin;S. Belinsky
通讯作者：
J. Issa;S. Baylin;S. Belinsky
DOI：
10.1073/pnas.96.22.12754
发表时间：
1999-10-26
影响因子：
11.1
作者：
Nuovo, GJ;Plaia, TW;Herman, JG
通讯作者：
Herman, JG
影响因子：
4.7
作者：
Belinsky, SA;Snow, SS;Palmisano, WA
通讯作者：
Palmisano, WA
影响因子：
3.5
作者：
Bestor, TH
通讯作者：
Bestor, TH
影响因子：
56.9
作者：
KAMB, A;GRUIS, NA;SKOLNICK, MH
通讯作者：
SKOLNICK, MH