Aquaporins mediate the chemoresistance of human melanoma cells to arsenite

Mol Oncol. 2012 Feb;6(1):81-7. doi: 10.1016/j.molonc.2011.11.001. Epub 2011 Nov 13.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Aquaporins / genetics
  • Aquaporins / metabolism*
  • Arsenites / pharmacology*
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Melanoma / genetics
  • Melanoma / pathology*

Substances

  • Aquaporins
  • Arsenites
  • arsenite