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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Atypical methylation of the interleukin-8 gene correlates strongly with the metastatic potential of breast carcinoma cells
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Atypical methylation of the interleukin-8 gene correlates strongly with the metastatic potential of breast carcinoma cells

机译：白细胞介素8基因的非典型甲基化与乳腺癌细胞的转移潜能密切相关

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摘要

Previously, we have shown that a strong correlation exists between the metastatic potential of breast carcinoma cell lines and their ectopic expression of IL-8. The undifferentiated, highly metastatic cell lines with high metastatic potential produce much more IL-8 than their differentiated lower metastatic counterparts. After eliminating the possibility that transcription factor activity was responsible for differences in IL-8 release, we examined the IL-8 gene for possible epigenetic modifications. Here, we report an aberrant methylation pattern that may be responsible for the differences in IL-8 release between the high and low metastatic cell lines. We determined that none of the deoxycytidylate-phosphate-deoxyguanylate (CpG) sites in the reported IL-8 promoter were methylated in either cell type. Much further upstream in the IL-8 gene, two CpG sites were identified that are differentially methylated. These two sites were fully methylated in the high metastatic cell lines, which produce large quantities of IL-8 and remain unmethylated in the low metastatic cell lines where the IL-8 gene is relatively silent. The DNA methylation results presented here differ from the common epigenetic paradigm in which methylation of promoter CpG islands silences gene expression, suggesting that there are additional epigenetic control mechanisms that as yet have not been fully appreciated or explored.
机译：以前，我们已经显示乳腺癌细胞系的转移潜能与其IL-8的异位表达之间存在很强的相关性。具有高转移潜力的未分化，高度转移细胞系比分化的较低转移对应物产生更多的IL-8。在消除转录因子活性导致IL-8释放差异的可能性后，我们检查了IL-8基因的可能表观遗传修饰。在这里，我们报告了异常的甲基化模式，这可能是高和低转移细胞系之间IL-8释放的差异所致。我们确定在报告的IL-8启动子中，任何一种细胞类型均未甲基化脱氧胞苷磷酸盐-磷酸-脱氧鸟苷酸（CpG）位点。在IL-8基因的更上游，确定了两个CpG位点被甲基化。这两个位点在高转移性细胞系中完全甲基化，产生大量的IL-8，而在低转移性细胞系中未甲基化，而IL-8基因相对沉默。这里介绍的DNA甲基化结果不同于普通的表观遗传范式，在后者中启动子CpG岛的甲基化使基因表达沉默，这表明尚有其他表观遗传控制机制尚未得到充分认识或探索。

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