SALL4 is essential for cancer cell proliferation and is overexpressed at early clinical stages in breast cancer
SALL4 is essential for cancer cell proliferation and is overexpressed at early clinical stages in breast cancer
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DOI：
10.3892/ijo.2011.929
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发表时间：
2011-04-01
影响因子：
5.2
通讯作者：
Watanabe, Naoki
中科院分区：
文献类型：
--
作者：
Kobayashi, Daisuke;Kuribayshi, Kageaki;Watanabe, Naoki
很少有靶分子被鉴定为能够以高灵敏度和特异性诊断乳腺癌，特别是在癌症的早期临床阶段。在这里，我们提出了第一个证据的诊断性能的基因表达的SALL 4，转录因子，在胚胎发育和胚胎干细胞（ES）的自我更新，在乳腺癌中起着至关重要的作用。SALL 4的敏感性和特异性分别为80.4%和80.0%，使用从受试者工作特征曲线分析获得的截止值进行估计。此外，来自同一乳腺癌患者的配对癌组织和非癌组织的比较显示，在86.1%（31/36）的标本中SALL 4 mRNA水平升高。临床病理因素与SALL 4 mRNA表达无明显相关性，但在早期临床阶段SALL 4 mRNA仍呈高水平表达。确定SALL 4表达的显著性的siRNA实验显示乳腺癌MCF 7细胞中的增殖完全抑制。siRNA的这种抑制作用是通过主要在G1期的细胞周期停滞诱导的，导致细胞体积增加。这些结果表明，SALL 4 mRNA可能是一个新的工具，以支持乳腺癌的诊断，它也可能代表一个新的治疗靶点。
Few target molecules have been identified that enable the diagnosis of breast cancer with a high sensitivity and specificity, especially in the early clinical stages of cancer. Here, we present the first evidence for diagnostic performance of gene expression for SALL4, a transcription factor that plays an essential role in the embryonic development and self-renewal of embryonic stem (ES) cells, in breast cancer. The sensitivity and specificity of SALL4 was 80.4 and 80.0%, respectively, as estimated using the cut-off value obtained from the analysis of the receiver operating characteristic curve. Furthermore, comparison of paired cancer and non-cancer tissues from the same breast cancer patient revealed elevated SALL4 mRNA levels in 86.1% (31/36) of the specimens. No obvious correlations were detected between clinicopathological factors and SALL4 mRNA expression; however, SALL4 mRNA was expressed at a high level even in the early clinical stages of the cancer. An siRNA experiment to determine the significance of SALL4 expression showed complete inhibition of proliferation in breast cancer MCF7 cells. This inhibitory effect of siRNA was induced by cell cycle arrest mainly at the G1 phase, leading to increased cell volume. These results suggest that SALL4 mRNA may be a new tool to support the diagnosis of breast cancer, and it may also represent a novel therapeutic target.