Critical role of aquaporin-3 in the human epidermal growth factor-induced migration and proliferation in the human gastric adenocarcinoma cells
Critical role of aquaporin-3 in the human epidermal growth factor-induced migration and proliferation in the human gastric adenocarcinoma cells
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DOI：
10.4161/cbt.9.12.11705
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发表时间：
2010-06-15
影响因子：
3.6
通讯作者：
Wu, Wenxi
中科院分区：
文献类型：
--
作者：
Huang, Yiming;Zhu, Zhengcai;Wu, Wenxi
背景：水通道蛋白（AQPs）在人类多种不同肿瘤细胞中表达。AQPs参与细胞迁移和增殖的新证据将AQPs添加到肿瘤生物学中不断扩大的效应物列表中。目的：探讨AQP3在人胃癌细胞系AGS和SGC7901中的表达是否能促进细胞迁移和增殖。结果：我们发现AQP3在人胃癌细胞系、AGS和SGC7901中均有表达。hEGF诱导AQP3表达呈时间和剂量依赖性，增加胃癌细胞的迁移和增殖。siRNA敲低AQP3抑制hegf诱导的AQP3表达，从而抑制细胞迁移和增殖。此外，丝裂原活化蛋白激酶(MEK)/细胞外信号调节激酶（ERK）抑制剂U0126抑制hegf诱导的AQP3表达和细胞迁移或增殖。方法：用人表皮生长因子（hEGF）处理培养的AGS或SGC7901细胞，进行细胞迁移实验和细胞增殖实验。western blot检测蛋白表达和活化水平。通过小干扰（si） RNA获得AQP3基因敲低。综上所述，我们的研究结果首次证明了AQP3在hEGF诱导的癌细胞迁移和增殖中起着关键作用，并且hEGF通过ERK信号转导途径诱导AQP3的表达。这些发现为AQP3在人胃癌中作为肿瘤生长和扩散的潜在重要决定因素的新作用提供了证据。
Background: Aquaporins (AQPs) are expressed in many different tumor cell types in human. New evidence for the involvement of AQPs in cell migration and proliferation adds AQPs to an expanding list of effectors in tumor biology.Aims: The aim of this study was to investigate whether AQP3 expression in the human gastric carcinoma cell lines, AGS and SGC7901, enhances cell migration and proliferation.Results: Here, we showed that AQP3 is expressed in the human gastric cancer cell lines, AGS and SGC7901. The hEGF induced AQP3 expression in a time-and dose-dependent manner and increased gastric cancer cell migration and proliferation. AQP3 knockdown by siRNA inhibited hEGF-induced AQP3 expression and thus cell migration and proliferation. Furthermore, a mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) inhibitor U0126 inhibited hEGF-induced AQP3 expression and cell migration or proliferation.Methods: Cultured AGS or SGC7901 cells were treated with human epidermal growth factor (hEGF) and subjected to cell migration assay and cell proliferation assay. The expression or activation level of proteins was analyzed by western blot. AQP3 knockdown was obtained by small interfering (si) RNA.Conclusions: Collectively, our findings provide for the first time that AQP3 plays a critical role in hEGF-induced cancer cell migration and proliferation and that hEGF induces AQP3 expression via ERK signal transduction pathways. These finds provide evidence for a novel role of AQP3 in human gastric carcinoma as a potentially important determinant of tumor growth and spread.