Global DNA hypomethylation suppresses squamous carcinogenesis in the tongue and esophagus
Global DNA hypomethylation suppresses squamous carcinogenesis in the tongue and esophagus
复制标题
DOI：
10.1111/j.1349-7006.2009.01171.x
复制
发表时间：
2009-07-01
期刊：
影响因子：
5.7
通讯作者：
Hara, Akira
中科院分区：
文献类型：
--
作者：
Baba, Seiji;Yamada, Yasuhiro;Hara, Akira
全基因组DNA低甲基化和伴随的位点特异性基因高甲基化是人类肿瘤中最常见的分子改变。先前的研究表明，DNA甲基化水平的遗传降低导致对肿瘤发展的相反影响，这取决于肿瘤细胞类型和肿瘤发生的不同阶段。例如，小鼠DNA甲基化水平的降低强烈抑制了肠道肿瘤的发展，而它们诱导了胸腺淋巴瘤和肝脏肿瘤。在本研究中，使用DNA甲基转移酶1（Dnmt 1）亚型等位基因，以减少基因组甲基化，我们研究了DNA低甲基化的影响，在舌头和食管鳞状细胞癌的诱导4-硝基喹啉1-氧化物。DNA甲基化水平的遗传降低导致舌和食管中肿瘤形成的抑制。组织学分析表明，DNA低甲基化优先抑制鳞状细胞癌的发展。结果表明，基因组低甲基化抑制舌和食管鳞状细胞癌的发生，并且表观遗传状态的药理学修饰可能有助于上消化道癌症的预防和治疗。（Cancer Sci 2009; 100：1186-1191）
Genome-wide DNA hypomethylation and concomitant site-specific gene hypermethylation are among the most common molecular alterations in human neoplasia. Previous studies revealed that genetic reduction of the DNA methylation level results in opposing effects on tumor development, depending on the tumor cell type and on the different stages of the tumorigenesis. For instance, reduced levels of DNA methylation in mice strongly inhibited tumor development of the intestine, whereas they induced thymic lymphomas and liver tumors. In the present study, using DNA methyltrasferase 1 (Dnmt1) hypomorphic alleles to reduce genomic methylation, we examined the effects of DNA hypomethylation on a murine squamous carcinogenesis in the tongue and esophagus induced by 4-nitroquinoline 1-oxide. Genetic reduction of DNA methylation level led to the suppression of tumor formation in both tongue and esophagus. Histological analyses revealed that DNA hypomethylation preferentially inhibited the development of squamous cell carcinomas. The results suggest that genomic hypomethylation inhibits squamous carcinogenesis in the tongue and esophagus, and that pharmacological modification of epigenetic status might be useful for the prevention and treatment of cancers in the upper digestive tract. (Cancer Sci 2009; 100: 1186-1191)