Department of Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi 409-3898, Japan.
Hum Pathol. 2012 Jun;43(6):834-42. doi: 10.1016/j.humpath.2011.07.009. Epub 2011 Sep 13.
Chromatin remodeling through histone modification is an important mechanism of epigenetic gene dysregulation in human cancers. However, little is known about global alteration of histone status during tumorigenesis and cancer progression. Histone H3 status was examined in benign and malignant colorectal tumors by immunohistochemistry and Western blotting. For immunohistochemical evaluation, 4 anti-histone H3 antibodies, specific to dimethylation at lysine 4 (H3K4me2), acetylation at lysine 9 (H3K9ac), dimethylation at lysine 9 (H3K9me2), and trimethylation at lysine 27 (H3K27me3), were used. On immunohistochemistry, H3K4me2, H3K9ac, and H3K27me3 showed no significant changes between normal and colorectal tumors. On the other hand, the global level of H3K9me2 was distinctly higher in neoplastic cells (adenoma and adenocarcinoma) than in normal glandular cells. In addition, it was significantly higher in adenocarcinoma than in adenoma. Correspondingly, Western blotting confirmed that H3K9me2 expression was significantly higher in adenocarcinomas than in normal colorectal mucosa. No alteration of H3K9me2 was observed with tumor differentiation and with the histological subtypes of colorectal cancers. These results suggest that aberration of the global H3K9me2 level is an important epigenetic event in colorectal tumorigenesis and carcinogenesis involved with gene regulation in neoplastic cells through chromatin remodeling.
通过组蛋白修饰进行染色质重塑是人类癌症中表观遗传基因失调的重要机制。然而，在肿瘤发生和癌症进展过程中，组蛋白状态的全局变化知之甚少。通过免疫组织化学和 Western blot 检测良性和恶性结直肠肿瘤中的组蛋白 H3 状态。对于免疫组织化学评估，使用了 4 种针对赖氨酸 4 位二甲基化（H3K4me2）、赖氨酸 9 位乙酰化（H3K9ac）、赖氨酸 9 位二甲基化（H3K9me2）和赖氨酸 27 位三甲基化（H3K27me3）的抗组蛋白 H3 抗体。免疫组织化学结果显示，H3K4me2、H3K9ac 和 H3K27me3 在正常和结直肠肿瘤之间没有明显变化。另一方面，H3K9me2 的全局水平在肿瘤细胞（腺瘤和腺癌）中明显高于正常腺细胞。此外，腺癌中的 H3K9me2 水平明显高于腺瘤。相应地，Western blot 证实 H3K9me2 在腺癌中的表达明显高于正常结直肠黏膜。H3K9me2 的改变与肿瘤分化和结直肠癌的组织学亚型无关。这些结果表明，全局 H3K9me2 水平的异常是结直肠肿瘤发生和癌变中的一个重要表观遗传事件，涉及通过染色质重塑调节肿瘤细胞中的基因。
