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出 处:《中国生物工程杂志》2008年第4期1-6,共6页China Biotechnology
基 金:国家"973"计划资助项目(2003CB716402)
摘 要:Twist是一个bHLH(basic Helix-loop-Helix)类型的转录因子,近年来研究发现,Twist在乳腺癌中的表达显著升高,并能促进乳腺癌的转移。为了探索Twist促进乳腺癌转移的分子机制,采用RNA干扰技术在小鼠乳腺癌细胞株4T1中沉默Twist的表达,通过全基因组基因芯片技术检测了Twist沉默前后4T1细胞基因表达谱的差异性。体内实验结果证明Twist表达被沉默后4T1细胞的肺转移能力明显被抑制。芯片结果表明:表达差异显著的基因有167条,其中与肿瘤相关的基因有26条,包括15条上调基因和11条下调基因。这些基因中可能存在能被Twist调控并与肿瘤转移相关的基因,为以后研究Twist影响乳腺癌转移的分子机制提供了帮助。Previous studies have revealed Twist, a basic helix-loop-helix transcription factor, plays an important role in breast cancer metastasis. To clarify the molecular mechanism of its involvement in cancer metastasis, Twist was silenced by RNAi in highly metastatic 4T1 cells. Then microarray chips were used to investigate the gene-expression pattern of the Twist-knockdown 4T1 cells and the normal 4T1 cells. The results indicated that silencing of Twist significantly suppressesed lung metastasis of 4T1 cells in vivo. Direct comparison of gene-expression profiles showed that 167 genes in Twist-knockdown cells differed dramatically in expression levels from those in control cells. Among the 167 genes, 26 well-known tumor-associated genes, including 15 upregulated and 11 down-regulated genes were found. These genes appear to be regulated by Twist during breast tumorigenesis. The findings provide new insights into the mechanism by which Twist is involved in tumorigenesis.
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