Chang Heng, Shi Yong-Hua, Talaf Tuo-Kan, Lin Chen
Urumqi General Hospital of Lanzhou Command, PLA Urumqi 830012, Xinjiang, China.
Department of Pathology, Basic Medicine College of Xinjiang Medical University Urumqi 830011, Xinjiang, China.
Int J Clin Exp Pathol. 2014 Oct 15;7(11):7663-71. eCollection 2014.
Abnormal expression of aquaporins (AQPs) has been reported in several human cancers. Epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinases1/2 (ERK1/2) are associated with tumorigenesis and cancer progression and may upregulate AQPs expression. In this study, we investigated acquaporin-8 expression and signaling via epidermal growth factor receptor-extracellular signal-regulated kinases1/2 in human esophageal cancer Eca-109 cells by western blot, immunofluorescence and wound healing (scratch) assays. Our results showed that epidermal growth factor (EGF) induced both Eca-109 migration and AQP8 expression. Wound healing results showed that cell migration was increased by 1.23-1.10-fold at 24 h and 48 h after EGF treatment. AQP8 expression was significantly increased (1.19-fold) at 48 h after EGF treatment in Eca-109. The EGFR kinase inhibitor, PD153035, blocked EGF-induced AQP8 expression and cell migration. AQP8 expression was decreased from 3.65-fold (EGF-treated) to 0.55-fold (PD153035-treated) in Eca-109. Furthermore, the MEK [MAPK (mitogen-activated protein kinase)/Erk1/2]/Erk1/2 inhibitor U0126 also inhibited EGF-induced AQP8 expression and cell migration. AQP8 expression was decreased from 3.92-fold (EGF-treated) to 1.38-fold (U0126-treated) in Eca-109. In conclusions, EGF induces AQP8 expression and cell migration in Eca-109 cells via the EGFR/Erk1/2 signal transduction pathway.
水通道蛋白（AQPs）的异常表达已在多种人类癌症中被报道。表皮生长因子受体（EGFR）-细胞外信号调节激酶1/2（ERK1/2）与肿瘤发生和癌症进展相关，可能上调AQPs的表达。在本研究中，我们通过蛋白质免疫印迹法、免疫荧光法和伤口愈合（划痕）试验，研究了人食管癌Eca-109细胞中aquaporin-8的表达以及通过表皮生长因子受体-细胞外信号调节激酶1/2的信号传导。我们的结果表明，表皮生长因子（EGF）诱导Eca-109细胞迁移和AQP8表达。伤口愈合结果显示，EGF处理后24小时和48小时，细胞迁移增加了1.23至1.10倍。EGF处理后48小时，Eca-109细胞中AQP8表达显著增加（1.19倍）。EGFR激酶抑制剂PD153035可阻断EGF诱导的AQP8表达和细胞迁移。在Eca-109细胞中，AQP8表达从3.65倍（EGF处理组）降至0.55倍（PD153035处理组）。此外，MEK [丝裂原活化蛋白激酶（MAPK）/Erk1/2]/Erk1/2抑制剂U0126也抑制EGF诱导的AQP8表达和细胞迁移。在Eca-109细胞中，AQP8表达从3.92倍（EGF处理组）降至1.38倍（U0126处理组）。总之，EGF通过EGFR/Erk1/2信号转导通路诱导Eca-109细胞中AQP8表达和细胞迁移。
