Hypermethylation leads to silencing of the SYK gene in human breast cancer.
Hypermethylation leads to silencing of the SYK gene in human breast cancer.
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发表时间：
2001-07
期刊：
影响因子：
11.2
通讯作者：
Yunfei Yuan;Richard Mendez;Aysegul A. Sahin;J. Dai
中科院分区：
文献类型：
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作者：
Yunfei Yuan;Richard Mendez;Aysegul A. Sahin;J. Dai
许多癌症相关基因已被证明在乳腺肿瘤发生期间通过CpG岛的超甲基化而失活。SYK是一种候选的肿瘤抑制因子，已发现在乳腺癌细胞系的一个子集中不表达，但SYK沉默的机制尚不清楚。在这项研究中，我们研究了乳腺癌细胞系和原发性乳腺癌组织中SYK基因的5' CpG岛甲基化状态。我们在30%（6/20）的乳腺癌细胞系中发现SYK 5' CpG高度甲基化，异常甲基化状态与SYK基因表达的缺失密切相关。用甲基化抑制剂5-氮杂-2 '-脱氧胞苷处理细胞，导致SYK阴性细胞中SYK表达的重新激活，如通过逆转录-PCR检测的。利用甲基化特异性PCR，我们证明SYK在32%（12/37）的乳腺癌中是高甲基化的，而所有匹配的邻近正常乳腺组织都表现出非甲基化的DNA状态。我们的结论是，SYK在乳腺癌中经常通过表观遗传途径失活。由于SYK已被证明是一种肿瘤抑制因子，并且其在乳腺癌中的表达缺失与肿瘤侵袭性相关，因此异常的SYK甲基化是导致表达缺失的原因，因此可能对肿瘤侵袭性起允许作用。
A number of cancer-associated genes have been shown to be inactivated by hypermethylation of CpG islands during breast tumorigenesis. SYK, a candidate tumor suppressor, has been found not expressed in a subset of breast cancer cell lines, but the mechanism by which SYK is silenced is unclear. In this study, we examined the 5' CpG island methylation status of the SYK gene in breast cancer cell lines and primary breast cancer tissues. We found SYK 5' CpG hypermethylation in 30% (6/20) of breast cancer cell lines, and the aberrant methylation status was strongly associated with loss of SYK gene expression. Treatment of cells with a methylation inhibitor, 5-aza-2'-deoxycytidine, led to a reactivation of SYK expression in SYK-negative cells, as detected by reverse transcription-PCR. Using methylation-specific PCR, we demonstrated that SYK is hypermethylated in 32% (12/37) of unselected breast tumors, whereas all of the matched neighboring normal breast tissues exhibited unmethylated DNA status. We concluded that SYK is frequently inactivated through an epigenetic pathway in breast cancer. Because SYK has been shown to function as a tumor suppressor, and its loss of expression in breast cancer has been correlated with tumor invasiveness, the aberrant SYK methylation is responsible for the loss of expression and may consequently play a permissive role for tumor aggressiveness.