The major vault protein mediates resistance to epidermal growth factor receptor inhibition in human hepatoma cells.

Cancer Lett 2012 Jun 17;319(2):164-172. Epub 2012 Jan 17.

Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria. Electronic address:

To better understand the response of HCC to EGFR inhibition, we analyzed factors connected to the resistance of HCC cells against gefitinib. Sensitive HCC3 cells co-expressed EGFR and ErbB3 but lacked kinase-domain mutations in EGFR. Interestingly, expression of MVP was restricted to resistant cell lines, whereas ABCB1 and ABCC1 showed no association with gefitinib resistance. Moreover, ectopic MVP expression in HCC3 cells decreased gefitinib sensitivity, increased AKT phosphorylation and reduced the expression of inflammatory pathway-associated genes, whereas silencing of MVP in Hep3B and HepG2 cells increased sensitivity. These findings suggest MVP as a novel player in resistance against EGFR inhibition.

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http://linkinghub.elsevier.com/retrieve/pii/S030438351200027
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http://dx.doi.org/10.1016/j.canlet.2012.01.002DOI Listing
June 2012
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