EGF induces cell motility and multi-drug resistance gene expression in breast cancer cells
EGF induces cell motility and multi-drug resistance gene expression in breast cancer cells
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DOI：
10.4161/cc.5.23.3535
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发表时间：
2006-12-01
期刊：
影响因子：
4.3
通讯作者：
McCubrey, James A.
中科院分区：
文献类型：
--
作者：
Garcia, Ruben;Franklin, Richard A.;McCubrey, James A.
表皮生长因子受体(EGFR)对正常发育、分化和细胞增殖具有重要作用。在乳腺癌中观察到了EGFR的去调控。由这些受体激活的EGFR和信号通路已经与乳腺癌的晚期肿瘤分期和不良的临床预后相关；然而，导致这一过程的确切机制仍不清楚。在这里，我们展示了EGF处理MCF-7乳腺癌细胞，激活Akt和ERK，诱导形态变化，并增加细胞运动性。此外，Raf-1的结构性表达和MEK抑制剂的使用证明了Raf/MEK/ERK通路参与了这些过程。重要的是，我们检测到EGF诱导了MRP-1、3、5和7基因的表达和MRP1启动子活性的增加。综上所述，在没有其他生长因子的情况下，EGF作用于MCF-7乳腺癌细胞，可导致EGFR信号转导通路的激活，这与细胞运动和耐药有关。
The epidermal growth factor receptor (EGFR) is important for normal development, differentiation, and cell proliferation. Deregulation of EGFR has been observed in breast cancer. EGFR and signal pathways activated by these receptors have been associated with an advanced tumor stage and a poor clinical prognosis in breast cancer; however, the precise mechanisms responsible for this process are still not known. Here we show that treatment of MCF-7 breast cancer cells with EGF activated Akt and ERK, induced morphological changes, and increased cell motility. In addition, the constitutive expression of Raf-1 and the use of a MEK inhibitor demonstrated the participation of the Raf/MEK/ERK pathway in these processes. Importantly we detected that EGF induced MRP- 1, 3, 5 and 7 gene expression and an increase in MRP1 promoter activity. In conclusion, treatment of MCF-7 breast cancer cells with EGF, in the absence of other growth factors, resulted in activation of EGFR signal transduction pathways; which were related with cell motility and drug resistance.