Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
J Gastroenterol. 2014 Apr;49(4):655-66. doi: 10.1007/s00535-013-0827-9. Epub 2013 May 9.
Aquaporins (AQPs) are water channel proteins that facilitate transcellular water movements. Recent studies have shown that AQP5 is expressed in various cancers, and plays a role in tumor progression. However, its expression and role in esophageal squamous cell carcinoma (ESCC) have not been investigated. We examined the pathophysiologic role of AQP5 in cell proliferation and survival, and also investigated its expression and effects on the prognosis of ESCC patients.
AQP5 expression in human ESCC cell lines was analyzed by Western blot testing. Knockdown experiments with AQP5 siRNA were conducted, and the effects on cell proliferation, cell cycle progression, and cell survival were analyzed. The cells' gene expression profiles were analyzed by microarray analysis. Immunohistochemistry of AQP5 for 68 primary tumor samples obtained from ESCC patients undergoing esophagectomy was performed.
AQP5 expression was high in TE2 and TE5 cells. In these cells, the knockdown of AQP5 using siRNA inhibited cell proliferation and G1-S phase progression, and induced apoptosis. The AQP5 siRNA transfected TE5 cells showed significant increase in p21 and decrease in CCND1 mRNA expression, respectively. The expression pattern of AQP5 and p21 protein was sharply contrasted, but AQP5 and CCND1 protein expression showed a similar pattern in ESCC tissue. These findings agree with the microarray results. Immunohistochemical staining of 68 ESCC patients showed the AQP5 expression is associated with tumor size, histological type, and tumor recurrence.
The AQP5 expression in ESCC cells may affect cell proliferation and survival, and impact on the prognosis of ESCC patients.
水通道蛋白（AQPs）是促进细胞间水运动的水通道蛋白。最近的研究表明，AQP5在各种癌症中表达，并在肿瘤进展中发挥作用。然而，其在食管鳞状细胞癌（ESCC）中的表达和作用尚未得到研究。我们研究了 AQP5 在细胞增殖和存活中的病理生理作用，并研究了其表达对 ESCC 患者预后的影响。
通过 Western blot 检测分析人 ESCC 细胞系中 AQP5 的表达。用 AQP5 siRNA 进行敲低实验，分析对细胞增殖、细胞周期进程和细胞存活的影响。通过微阵列分析分析细胞的基因表达谱。对 68 例接受食管癌切除术的 ESCC 患者的原发肿瘤样本进行 AQP5 的免疫组织化学染色。
AQP5 在 TE2 和 TE5 细胞中表达较高。在这些细胞中，用 siRNA 敲低 AQP5 抑制细胞增殖和 G1-S 期进程，并诱导细胞凋亡。AQP5 siRNA 转染的 TE5 细胞中 p21 的表达显著增加，CCND1mRNA 的表达分别显著降低。AQP5 和 p21 蛋白的表达模式形成鲜明对比，但 ESCC 组织中 AQP5 和 CCND1 蛋白的表达模式相似。这些发现与微阵列结果一致。对 68 例 ESCC 患者的免疫组化染色显示，AQP5 的表达与肿瘤大小、组织学类型和肿瘤复发有关。
ESCC 细胞中 AQP5 的表达可能影响细胞增殖和存活，并影响 ESCC 患者的预后。
