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

Cancer Lett. 2012 Jun 28;319(2):164-172. doi: 10.1016/j.canlet.2012.01.002. Epub 2012 Jan 17.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Hepatocellular / drug therapy*
  • Cell Line, Tumor
  • Cytokines
  • Drug Resistance, Neoplasm / drug effects*
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics
  • Gefitinib
  • Humans
  • Liver Neoplasms / drug therapy*
  • Protein Kinase Inhibitors / pharmacology*
  • Quinazolines / pharmacology*
  • RNA, Small Interfering / pharmacology
  • Signal Transduction / drug effects
  • Vault Ribonucleoprotein Particles / physiology*


  • Antineoplastic Agents
  • Cytokines
  • Protein Kinase Inhibitors
  • Quinazolines
  • RNA, Small Interfering
  • TRANK1 protein, human
  • Vault Ribonucleoprotein Particles
  • major vault protein
  • ErbB Receptors
  • Gefitinib