Tropomyosin-1, a novel suppressor of cellular transformation is downregulated by promoter methylation in cancer cells
Tropomyosin-1, a novel suppressor of cellular transformation is downregulated by promoter methylation in cancer cells
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DOI：
10.1016/s0304-3835(02)00119-2
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发表时间：
2002-09-26
期刊：
影响因子：
9.7
通讯作者：
Prasad, GL
中科院分区：
文献类型：
--
作者：
Bharadwaj, S;Prasad, GL
原肌球蛋白（TMs）是一类微丝结合蛋白，在转化细胞中被抑制。我们研究了乳腺癌细胞中TMs的抑制机制，特别是原肌球蛋白-1 （TM1）的抑制机制。单独用5-aza-2′-脱氧胞苷（AZA）抑制DNA甲基转移酶不诱导TM1表达。然而，曲古抑素A （TSA）和AZA联合治疗可以检测到TM1的表达，但不能检测到其他TM亚型的表达。TM1表达的上调与含有微丝的TM1的重新出现和不依赖锚定生长的消除是平行的。在ras转化成纤维细胞中，AZA和TSA在TM1基因再激活中的协同作用也很明显。这些数据首次表明，TM1基因的高甲基化和染色质重塑是乳腺癌细胞中TM1表达下调的主要机制。(C) 2002爱思唯尔科学爱尔兰有限公司版权所有。
Tropomyosins (TMs) are a family of microfilament binding proteins, which are suppressed in the transformed cells. We have investigated the mechanism of suppression of TMs, in particular that of tropomyosin-1 (TM1), in breast cancer cells. Inhibition of DNA methyl transferase with 5-aza-2'-deoxycytidine (AZA) alone did not induce TM1 expression. However, combined treatment of trichostatin A (TSA) and AZA resulted in readily detectable expression of TM1, but not that of other TM isoforms. Upregulation of TM1 expression paralleled with the reemergence of TM1 containing microfilaments, and in abolition of anchorage-independent growth. The synergistic action of AZA and TSA in reactivation of TM1 gene was also evident in ras-transformed fibroblasts. These data, for the first time, show that hypermethylation of TM1 gene and chromatin remodeling are the predominant mechanisms by which TM1 expression is downregulated in breast cancer cells. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.