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Aquaporins mediate the chemoresistance of human melanoma cells to arsenite
Authors:Gao Lin  Gao Yanhui  Li Xiaobo  Howell Paul  Kumar Rajeev  Su Xiulan  Vlassov Alexander V  Piazza Gary A  Riker Adam I  Sun Dianjun  Xi Yaguang
Affiliation:Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, China.
Abstract:The integral membrane channel protein aquaporin (AQP) is aberrantly expressed with oncogenic characteristics in various human cancers. In this study, we analyzed the expression pattern of all subtypes of AQPs, and found that 8 out of 13 AQPs expressed in melanoma cells. To understand the role of aberrant expression of AQP in this disease, we over-expressed AQP3 and AQP9 in human melanoma WM266.4 cells and found that both AQPs significantly increased the chemoresistance of WM266.4 cells to arsenite. Functional studies showed that AQP3 and AQP9 can inhibit cell apoptosis induced by arsenite through down-regulating p53 and up-regulating Bcl-2 and XIAP. Our data suggest the implication of APQ in melanoma progression and that the over-expression of AQP3 and AQP9 contributes to the chemoresistance of melanoma to arsenite.
Keywords:AQP   Melanoma   Arsenite   Chemotherapy
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