Department of Medicine, Division of Nephrology, University Clinic of Wuerzburg, Wuerzburg, Germany.
Oncol Rep. 2010 Jan;23(1):183-9.
Loss of proliferative control and failure to undergo cellular differentiation are key events during carcinogenesis. We recently identified a new potential tumor suppressor gene named MTUS1 (mitochondrial tumor suppressor 1), down-regulated in undifferentiated tumor cell lines, inhibiting tumor cell proliferation after recombinant over-expression. The aim of this study was to investigate whether MTUS1 is also down-regulated in human tumor tissues, and whether reduced expression of MTUS1 enhances cellular proliferation. Expression of MTUS1 in human colon cancer tissues was compared with corresponding normal colon tissues using Western blot analysis and RT-PCR. Investigation of the DNA sequence and methylation pattern was performed using bisulfite reaction and DNA sequencing. Promotor activity was measured by promoter assays. Silencing of MTUS1 was carried out by siRNA transfection. Proliferation was measured by cell count. MTUS1 expression is significantly down-regulated in colon cancer tissues, compared to the corresponding normal tissues, on protein and mRNA level. No mutations of MTUS1 were detected in the coding sequence or the predicted promoter region in cancer tissues. No difference of CpG methylation, but an altered CpNpG methylation was found in the predicted promoter region. Functional significance of the predicted promoter region was demonstrated by promoter assays. Down-regulation of the MTUS1 expression by siRNA transfection significantly increased cellular proliferation. This study demonstrates a significant down-regulation of the MTUS1 expression in human colon cancer tissues. Since reduced expression of MTUS1 results in increased cellular proliferation, these data suggest that MTUS1 could be involved in the loss of proliferative control in human colon cancer.
失去增殖控制和不能进行细胞分化是癌变过程中的关键事件。我们最近鉴定了一个新的潜在肿瘤抑制基因，命名为 MTUS1（线粒体肿瘤抑制因子 1），在未分化的肿瘤细胞系中下调，重组过表达后抑制肿瘤细胞增殖。本研究的目的是研究 MTUS1 是否也在人类肿瘤组织中下调，以及 MTUS1 表达的降低是否增强了细胞增殖。使用 Western blot 分析和 RT-PCR 比较了 MTUS1 在人结肠癌组织和相应正常结肠组织中的表达。使用亚硫酸氢盐反应和 DNA 测序进行 DNA 序列和甲基化模式的研究。通过启动子测定测量启动子活性。通过 siRNA 转染沉默 MTUS1。通过细胞计数测量增殖。与相应的正常组织相比，结肠癌组织中 MTUS1 的表达在蛋白质和 mRNA 水平上均显著下调。在癌症组织中未检测到 MTUS1 编码序列或预测启动子区域的突变。在预测的启动子区域中发现 CpG 甲基化没有差异，但 CpNpG 甲基化发生改变。通过启动子测定证明了预测启动子区域的功能意义。通过 siRNA 转染下调 MTUS1 的表达显著增加了细胞增殖。本研究表明 MTUS1 在人结肠癌组织中表达显著下调。由于 MTUS1 表达的降低导致细胞增殖增加，这些数据表明 MTUS1 可能参与了人结肠癌中增殖控制的丧失。
