Methylation and silencing of the Thrombospondin-1 promoter in human cancer
Methylation and silencing of the Thrombospondin-1 promoter in human cancer
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DOI：
10.1038/sj.onc.1202663
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发表时间：
1999-05-27
期刊：
影响因子：
8
通讯作者：
Issa, JPJ
中科院分区：
文献类型：
--
作者：
Li, Q;Ahuja, N;Issa, JPJ
新生血管形成是许多人类癌症的共同特征，但在调节血管形成的基因中已证实相对较少的分子缺陷。血小板反应蛋白-1（Thrombospondin-1，THBS 1）是一种P53和Rb调控的血管生成抑制剂，在包括多形性胶质母细胞瘤（GBM）在内的一些人类肿瘤中已观察到其表达减少。为了研究甲基化相关的失活是否参与下调癌症中THBS 1的表达，我们分析了几种细胞系和原发性肿瘤中THBS 1的甲基化状态。三种细胞系（RKO、CEM和RAJI）在THBS 1 5' CpG岛内的几个CpG位点上完全甲基化，并且在RT-PCR中没有可检测到的表达，THBS 1表达在所有三个系中被甲基化抑制剂5-脱氧氮杂胞苷重新激活。此外，THBS 1甲基化存在于33%（14/42）的原发性GBM中，因此，从头甲基化可能是抑制THBS 1在人类肿瘤中表达的潜在途径。
Neovascularization is a common feature of many human cancers, but relatively few molecular defects have been demonstrated in genes regulating angiogenesis. Decreased expression of Thrombospondin-1 (THBS1), a P53 and Rb regulated angiogenesis inhibitor, has been observed in some human tumors, including glioblastoma multiforme (GBM). To study whether methylation-associated inactivation is involved in down-regulating THBS1 expression in cancer, we analysed the methylation status of THBS1 in several cell lines and primary tumors. Three cell lines (RKO, CEM and RAJI) were completely methylated at several CpG sites within the THBS1 5' CpG island, and had no detectable expression ba RT-PCR, THBS1 expression,vas readily reactivated using the methylation-inhibitor 5-deoxy-azacytidine in all three lines, Furthermore, THBS1 methylation was present in 33% (14/42) of primary GBMs, Thus, de novo methylation may serve as a potential way to inactivate THBS1 expression in human neoplasms.