362

AQP5

aquaporin 5;AQP5;aquaporin 5

aquaporin-5

12q13

protein-coding

Aquaporin (AQP) is a family of transmembrane proteins for water transport. Recent studies revealed that AQPs are likely to play a role in tumor progression and invasion. We aimed to examine the potential role of AQP5 in the progression of human breast cancer cells. expression of AQP5 mRNA and protein was seen in human breast cancer cell line (both MCF7 and MDA-MB-231) by RT-PCR and immunoblotting analysis. Immunoperoxidase labeling of AQP5 was observed at ductal epithelial cells of human breast tissues. In benign tumor, AQP5 labeling was mainly seen at the apical domains of ductal epithelial cells. In contrast, in invasive ductal carcinoma, prominent AQP5 labeling was associated with cancer cells, whereas some ducts were unlabeled and apical polarity of AQP5 in ducts was lost. Cell proliferation (BrdU incorporation assay) and migration of MCF7 cells were significantly attenuated by lentivirus-mediated AQP5-shRNA transduction. Hyperosmotic stress induced by sorbitol treatment (100 mM, 24 h) reduced AQP5 expression in MCF7 cells, which was also associated with a significant reduction in cell proliferation and migration. Taken together, prominent AQP5 expression in breast cancer cells with the loss of polarity of ductal epithelial cells was seen during the progression of breast carcinoma. shRNA- or hyperosmotic stress-induced reduction in AQP5 expression of MCF7 cells was associated with significantly reduced cell proliferation and migration. In conclusion, AQP5 overexpression is likely to play a role in cell growth and metastasis of human breast cancer and could be a novel target for anti-breast cancer treatment.

BACKGROUND: New evidence for involvement of aquaporins (AQPs) in cell migration and proliferation adds AQPs to an expanding list of effectors in tumor biology. But there is few report concerning the expression and role of AQPs in human gastric carcinogenesis so far. The aim of this current study was to investigate the expression profile of AQPs in human gastric carcinoma and its significance. METHODS: We screened the expression profile of AQP0 approximately AQP12 in gastric adenocarcinoma tissues and corresponding normal mucosa from 89 patients with gastric cancer by reverse transcriptase polymerase chain reaction (RT-PCR), Western blot analysis and immunochemical assay. The relationship between AQPs expression and clinicopathologic characteristics of patients was evaluated. RESULTS: Based on RT-PCR of 13 AQPs examined, AQP1, 3, 4, 5 and 11 were expressed in human gastric cancers or normal gastric tissues, and AQP3, 4 and 5 exhibited differential expression between human gastric carcinomas and corresponding normal tissues, which was confirmed by Western blot analyses. Immunohistochemical assay showed that AQP4 protein was expressed mainly in the membrane of parietal cell and chief cell in the normal gastric mucosa, and absent in carcinoma tissues. AQP3 and AQP5 were detected remarkably stronger in the carcinoma tissues than that in normal mucosa by immunofluorescence. AQP3 expression in cases with undifferentiated tumor was more than that in cases with well-differentiated tumor. Both AQP3 and AQP5 expression were associated with lymph node metastasis and lymphovascular invasion in patients. CONCLUSIONS: These findings of differential expressions of AQPs and their correlation with clinicopathologic characteristics implicated AQPs might play a role in human gastric carcinogenesis.