title: The major vault protein mediates resistance to epidermal growth factor receptor inhibition in human hepatoma cells.
abstract: 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.
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Losert
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Lötsch
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lackner
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Herwig
authors.initials: H
authors.lastname: Koppensteiner
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Peter-Vörösmarty
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Steiner
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Klaus
authors.initials: K
authors.lastname: Holzmann
authors.affiliation: Division of Oncology, Department of Medicine I, Medical University of Vienna, Währingergürtel 18-20, A-1090 Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Grunt
authors.affiliation: Department of Pathology, Medical University of Vienna, Währingergürtel 18-20, A-1090 Vienna, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schmid
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Marian
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Bettina
authors.initials: B
authors.lastname: Grasl-Kraupp
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Rolf
authors.initials: R
authors.lastname: Schulte-Hermann
authors.affiliation: Department of Pathology, Medical University of Vienna, Währingergürtel 18-20, A-1090 Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Krupitza
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Berger
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria. Electronic address: michael.grusch@meduniwien.ac.at.
authors.forename: Michael
authors.initials: M
authors.lastname: Grusch
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D045744:Cell Line, Tumor; D016207:Cytokines; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D000077156:Gefitinib; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D020394:Vault Ribonucleoprotein Particles / Q000502:physiology*; D000099187:Major Vault Protein
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D066246:ErbB Receptors; D000077156:Gefitinib; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D034741:RNA, Small Interfering; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C112841:TRANK1 protein, human