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

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• 作者：Annemarie Losert^a ; ¹ ; Daniela Lö ; tsch^a ; ¹ ; Andreas Lackner^a ; Herwig Koppensteiner^a ; Barbara Peter-Vö ; rö ; smarty^a ; Elisabeth Steiner^a ; Klaus Holzmann^a ; Thomas Grunt^b ; Katharina Schmid^c ; Brigitte Marian^a ; Bettina Grasl-Kraupp^a ; Rolf Schulte-Hermann^a ; Georg Krupitza^c ; Walter Berger^a ; Michael Grusch^a ; ^{michael.grusch@meduniwien.ac.at}
• 关键词：Hepatocellular carcinoma ; Epidermal growth factor receptor ; Gefitinib resistance ; Major vault protein
• 刊名：Cancer Letters
• 出版年：2012
• 期刊代码：44_03043835
• 类别：med
• 出版时间：28 June, 2012
• 卷：319
• 期：2
• 页码：164-172
• 文件大小：684 K

摘要

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.