Journal Article

Expression and functional role of vacuolar H<sup>+</sup>-ATPase in human hepatocellular carcinoma

Jingyu Xu, Rui Xie, Xuemei Liu, Guorong Wen, Hai Jin, Zhihao Yu, Yixia Jiang, Zhenglan Zhao, Yuan Yang, Bei Ji, Hui Dong and Biguang Tuo

in Carcinogenesis

Volume 33, issue 12, pages 2432-2440
Published in print December 2012 | ISSN: 0143-3334
Published online September 2012 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgs277
Expression and functional role of vacuolar H+-ATPase in human hepatocellular carcinoma

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Tumor cells often exist in a hypoxic microenvironment, which produces acidic metabolites. To survive in this harsh environment, tumor cells must exhibit a dynamic cytosolic pH regulatory system. Vacuolar H + -adenosine triphosphatase (V-ATPase) is considered to play an important role in the regulation of the acidic microenvironment of some tumors. In this study, we made an investigation on the expression and functional role of V-ATPase in native human hepatocellular carcinoma (HCC). The results showed that the messenger RNA and protein expression levels of V-ATPase subunit ATP6L in native human HCC tissues were markedly increased, compared with normal liver tissues. Immunohistochemical analysis further confirmed the enhanced expression of V-ATPase ATP6L in human HCC cells and revealed that V-ATPase ATP6L was distributed in the cytoplasm and plasma membrane of HCC cells. The results from immunofluorescence and biotinylation of cell surface protein showed that V-ATPase ATP6L was conspicuously located in the plasma membrane of human HCC cells. Bafilomycin A1, a specific V-ATPase inhibitor, markedly slowed the intracellular pH (pHi) recovery after acid load in human HCC cells and retarded the growth of human HCC in orthotopic xenograft model. These results demonstrated that V-ATPase is up-regulated in human HCC and involved in the regulation of pHi of human HCC cells. The inhibition of V-ATPase can effectively retard the growth of HCC, indicating that V-ATPase may play an important role in the development and progression of human HCC, and targeting V-ATPase may be a promising therapeutic strategy against human HCC.

Journal Article.  6307 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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