癌变
胚胎干细胞
生物
印记(心理学)
细胞生物学
癌症研究
DNA甲基化
恶性转化
干细胞
分子生物学
遗传学
基因
基因表达
作者
Teresa M. Holm,Laurie Jackson-Grusby,Tobias Brambrink,Yasuhiro Yamada,William M. Rideout,Rudolf Jaenisch
出处
期刊:Cancer Cell
[Elsevier]
日期:2005-10-01
卷期号:8 (4): 275-285
被引量:241
标识
DOI:10.1016/j.ccr.2005.09.007
摘要
Loss of imprinting (LOI), commonly observed in human tumors, refers to loss of monoallelic gene regulation normally conferred by parent-of-origin-specific DNA methylation. To test the function of LOI in tumorigenesis, we developed a model by using transient demethylation to generate imprint-free mouse embryonic stem cells (IF-ES cells). Embryonic fibroblasts derived from IF-ES cells (IF-MEFs) display TGFbeta resistance and reduced p19 and p53 expression and form tumors in SCID mice. IF-MEFs exhibit spontaneous immortalization and cooperate with H-Ras in cellular transformation. Chimeric animals derived from IF-ES cells develop multiple tumors arising from the injected IF-ES cells within 12 months. These data demonstrate that LOI alone can predispose cells to tumorigenesis and identify a pathway through which immortality conferred by LOI lowers the threshold for transformation.
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