Arsenicals produce stable progressive changes in DNA methylation patterns that are linked to malignant transformation of immortalized urothelial cells.
Arsenicals produce stable progressive changes in DNA methylation patterns that are linked to malignant transformation of immortalized urothelial cells.
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DOI：
10.1016/j.taap.2009.08.019
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发表时间：
2009-12-01
影响因子：
3.8
通讯作者：
Futscher BW
中科院分区：
文献类型：
--
作者：
Jensen TJ;Novak P;Wnek SM;Gandolfi AJ;Futscher BW
异常DNA甲基化参与癌发生，是肿瘤细胞的分子标志。肿瘤细胞通常表现出DNA甲基化的重新分布，导致全局低甲基化和区域高甲基化;然而，这些变化出现的速度尚未完全阐明，可能取决于细胞在从正常、有限寿命到恶性转化的路径中的时间位置。我们使用砷诱导的永生化人尿路上皮细胞恶性转化模型和DNA甲基化微阵列来研究从永生转化为恶性转化过程中发生的DNA甲基化变化的程度和时间性质。我们的数据表明，在砷诱导的恶性转化，异常的DNA甲基化发生非随机的，在数百个基因启动子逐渐进展，改变相关基因的表达，这些变化是符合收购的恶性性质，如锚定独立的生长和肿瘤形成免疫功能低下的小鼠。DNA甲基化的变化似乎是稳定的，因为从转化砷中取出的恶性转化细胞在DNA甲基化水平、相关基因表达或恶性表型方面没有逆转。这些数据表明，砷剂作为表观诱变剂，并直接链接到他们的能力，诱导恶性转化的表观基因组上的行动。
Aberrant DNA methylation participates in carcinogenesis and is a molecular hallmark of a tumor cell. Tumor cells generally exhibit a redistribution of DNA methylation resulting in global hypomethylation with regional hypermethylation; however, the speed in which these changes emerge has not been fully elucidated and may depend on the temporal location of the cell in the path from normal, finite lifespan to malignant transformation. We used a model of arsenical-induced malignant transformation of immortalized human urothelial cells and DNA methylation microarrays to examine the extent and temporal nature of changes in DNA methylation that occur during the transition from immortal to malignantly transformed. Our data presented herein suggest that during arsenical-induced malignant transformation, aberrant DNA methylation occurs non-randomly, progresses gradually at hundreds of gene promoters, alters expression of the associated gene, and these changes are coincident with the acquisition of malignant properties, such as anchorage independent growth and tumor formation in immunocompromised mice. The DNA methylation changes appear stable, since malignantly transformed cells removed from the transforming arsenical exhibited no reversion in DNA methylation levels, associated gene expression, or malignant phenotype. These data suggest that arsenicals act as epimutagens and directly link their ability to induce malignant transformation to their actions on the epigenome.
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影响因子：
4.3
作者：
Garbe, James C.;Holst, Charles R.;Stampfer, Martha R.
通讯作者：
Stampfer, Martha R.
影响因子：
10.3
作者：
Marshall, Guillermo;Ferreccio, Catterina;Smith, Allan H.
通讯作者：
Smith, Allan H.
影响因子：
14.9
作者：
Coolen, Marcel W;Statham, Aaron L;Gardiner-Garden, Margaret;Clark, Susan J
通讯作者：
Clark, Susan J
影响因子：
30.8
作者：
Jones, PL;Veenstra, GJC;Wolffe, AP
通讯作者：
Wolffe, AP
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y