Suppression of intestinal neoplasia by deletion of Dnmt3b
Suppression of intestinal neoplasia by deletion of Dnmt3b
复制标题
DOI：
10.1128/mcb.26.8.2976-2983.2006
复制
发表时间：
2006-04-01
影响因子：
5.3
通讯作者：
Jaenisch, R
中科院分区：
文献类型：
--
作者：
Lin, HJ;Yamada, Y;Jaenisch, R
伴随DNA甲基化的异常基因沉默与许多肿瘤的肿瘤进展相关，这些肿瘤也显示DNA甲基化的整体丢失。在Apc 4（Min/+）小鼠中使用从头甲基转移酶Dnmt 3b的条件失活，我们证明Dnmt 3b的丢失对微腺瘤形成没有影响，微腺瘤被认为是肠道肿瘤形成的最早阶段。然而，我们观察到肉眼可见的结肠腺瘤的形成显著减少。有趣的是，许多大的腺瘤显示Dnmt 3b失活的区域，表明Dnmt 3b是宏观腺瘤的初始生长所需的，但不是它们的维持所需的。这些结果支持Dnmt 3b在微腺瘤形成和宏观结肠肿瘤生长之间的过渡阶段中的作用，并进一步表明Dnmt 3b以及通过扩展从头甲基化在该过渡阶段发生后不需要维持肿瘤生长。
Aberrant gene silencing accompanied by DNA methylation is associated with neoplastic progression in many tumors that also show global loss of DNA methylation. Using conditional inactivation of de novo methyltransferase Dnmt3b in Apc4(Min/+) mice, we demonstrate that the loss of Dnmt3b has no impact on microadenoma formation, which is considered the earliest stage of intestinal tumor formation. Nevertheless, we observed a significant decrease in the formation of macroscopic colonic adenomas. Interestingly, many large adenomas showed regions with Dnmt3b inactivation, indicating that Dnmt3b is required for initial outgrowth of macroscopic adenomas but is not required for their maintenance. These results support a role for Dnmt3b in the transition stage between microadenoma formation and macroscopic colonic tumor growth and further suggest that Dnmt3b, and by extension de novo methylation, is not required for maintaining tumor growth after this transition stage has occurred.