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首页> 外文期刊>Pathobiology: journal of immunopathology, molecular and cellular biology >MBD2-mediated transcriptional repression of the p14ARF tumor suppressor gene in human colon cancer cells.
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MBD2-mediated transcriptional repression of the p14ARF tumor suppressor gene in human colon cancer cells.

机译：MBD2介导的人类结肠癌细胞p14ARF抑癌基因的转录抑制。

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OBJECTIVE: The p14(ARF) and p16(INK4A) tumor suppressor genes are commonly inactivated by aberrant methylation of their promoter regions in human colon cancer. The methyl-CpG-binding domain protein MBD2 is physically associated with the methylated promoters of the p14(ARF) and p16(INK4A) genes in specific tumor cell lines. Moreover, deficiency of MBD2 strongly inhibits intestinal tumorigenesis in the Min mouse, raising the possibility that the protein might be involved in transcriptional repression of methylated tumor suppressor genes. The aim of this study was to evaluate the role of MBD2 in the silencing of p14(ARF) and p16(INK4A) in cancer. METHODS: The MBD2 protein was stably knocked down by RNA interference in RKO, a colon cancer cell line in which both p14(ARF) and p16(INK4A) are silenced by methylation. RESULTS: We demonstrate here that MBD2 associates with the methylated promoter of the p14(ARF) gene in the RKO colon cancer cell line. Depletion of MBD2 by RNAi leads to selective upregulation ofthe p14(ARF) but not the p16(INK4A) gene transcript. In addition, p14(ARF) repression can be restored by expressing mouse MBD2 protein in MBD2-deficient RKO cells. CONCLUSION: These findings implicate MBD2 in transcriptional repression of the methylated p14(ARF) tumor suppressor gene and suggest that repression by MBD2 selectively affects a subset of methylated promoters.
机译：目的：在人类结肠癌中，p14（ARF）和p16（INK4A）抑癌基因通常通过其启动子区域的异常甲基化而失活。甲基CpG结合域蛋白MBD2与特定肿瘤细胞系中p14（ARF）和p16（INK4A）基因的甲基化启动子物理相关。此外，MBD2的缺乏会强烈抑制Min小鼠的肠道肿瘤发生，从而增加了该蛋白可能参与甲基化抑癌基因转录抑制的可能性。这项研究的目的是评估MBD2在癌症中p14（ARF）和p16（INK4A）沉默中的作用。方法：MBD2蛋白被RKO稳定地敲低，RKO是一种结肠癌细胞系，其中p14（ARF）和p16（INK4A）被甲基化沉默。结果：我们在这里证明MBD2与RKO结肠癌细胞系中p14（ARF）基因的甲基化启动子相关。 RNAi对MBD2的消耗导致p14（ARF）选择性上调，而p16（INK4A）基因转录本没有选择性上调。此外，可以通过在缺乏MBD2的RKO细胞中表达小鼠MBD2蛋白来恢复p14（ARF）抑制。结论：这些发现暗示MBD2参与甲基化的p14（ARF）肿瘤抑制基因的转录抑制，并暗示MBD2的抑制作用选择性地影响了甲基化启动子的一部分。

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