Background: 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.
Methods: 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.
Results: 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.
Conclusion: The AQP5 expression in ESCC cells may affect cell proliferation and survival, and impact on the prognosis of ESCC patients.