Oncogenic role of DDX3 in breast cancer biogenesis
Oncogenic role of DDX3 in breast cancer biogenesis
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DOI：
10.1038/onc.2008.33
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发表时间：
2008-06-01
期刊：
影响因子：
8
通讯作者：
Raman, V.
中科院分区：
文献类型：
--
作者：
Botlagunta, M.;Vesuna, F.;Raman, V.
苯并[a]芘二醇环氧化物(BPDE)是烟草烟雾中苯并[a]芘的活性代谢物，是一种主要的致癌化合物。为了评价BPDE对人乳腺上皮细胞的影响，我们将永生化的人乳腺细胞系MCF 10A暴露于BPDE中，并对其基因表达谱进行了研究。在表达的差异基因中，我们发现了死盒RNA解旋酶家族成员DDX3的一致激活。在MCF 10A细胞中过表达DDX3可诱导上皮样-间充质样转化，表现出更强的运动性和侵袭性，并在软琼脂实验中形成集落。免疫印迹和E-钙粘蛋白启动子报告实验均表明，除了表型改变外，MCF 10A-DDX3细胞还抑制了E-钙粘蛋白的表达。此外，染色质免疫沉淀法证实了DDX3与E-钙粘附素启动子在体内的关联。综上所述，这些结果表明，BPDE激活DDX3，可以促进乳腺上皮细胞的生长、增殖和肿瘤转化。
Benzo[a] pyrene diol epoxide (BPDE), the active metabolite of benzo[a] pyrene present in tobacco smoke, is a major cancer-causing compound. To evaluate the effects of BPDE on human breast epithelial cells, we exposed an immortalized human breast cell line, MCF 10A, to BPDE and characterized the gene expression pattern. Of the differential genes expressed, we found consistent activation of DDX3, a member of the DEAD box RNA helicase family. Overexpression of DDX3 in MCF 10A cells induced an epithelial-mesenchymal- like transformation, exhibited increased motility and invasive properties, and formed colonies in soft-agar assays. Besides the altered phenotype, MCF 10A-DDX3 cells repressed E-cadherin expression as demonstrated by both immunoblots and by E-cadherin promoter-reporter assays. In addition, an in vivo association of DDX3 and the E-cadherin promoter was demonstrated by chromatin immunoprecipitation assays. Collectively, these results demonstrate that the activation of DDX3 by BPDE, can promote growth, proliferation and neoplastic transformation of breast epithelial cells.