Aquaporins (AQPs) are water channel proteins expressed in various organs and tissues. So far abnormal expression of AQPs has been reported in several cancer tissues, but the function of AQP in human cancer has been little known. Here, we compared the protein expression levels of AQP3, 4 and 5 between human gastric cancer tissue and its accompanying normal mucosa in the upper or middle part of the stomach. It was found that AQP5 was significantly upregulated in the intestinal type of gastric adenocarcinomas but not in diffuse type of adenocarcinomas. AQP5 was localized in the apical membrane of the cancer cells. Expression of AQP4 was down-regulated both in intestinal and diffuse types of adenocarcinomas. No significant expression of AQP3 was observed in the cancer and normal tissues. To clarify the function of AQP5 in gastric adenocarcinomas, we transiently expressed AQP5 in a poorly differentiated human gastric adenocarcinoma cell line (MKN45). Interestingly, AQP5-expressing cell increased the number of differentiated cells. The AQP5 expression increased an activity of alkaline phosphatase, a marker for the intestinal epithelial cell type of cancer cells and expression level of laminin, an epithelial cell marker. Upregulation of AQP5 may be involved in the tumor differentiation of human stomach. [J Physiol Sci. 2007;57 Suppl:S77]