Correlation of gene expression of ATP-binding cassette protein and tyrosine kinase signaling pathway in patients with hepatocellular carcinoma

• Verfasst von: Hoffmann, Katrin [VerfasserIn]
• Verfasst von: Longerich, Thomas [VerfasserIn]
• Verfasst von: Büchler, Markus W. [VerfasserIn]
• Verfasst von: Schemmer, Peter [VerfasserIn]
• Verfasst von: Lin, Shibo [VerfasserIn]
• Verfasst von: Xiao, Zhi [VerfasserIn]
• Titel: Correlation of gene expression of ATP-binding cassette protein and tyrosine kinase signaling pathway in patients with hepatocellular carcinoma
• Verf.angabe: Katrin Hoffmann, Lin Shibo, Zhi Xiao, Thomas Longerich, Markus W. Büchler and Peter Schemmer
• E-Jahr: 2011
• Jahr: [November 2011]
• Umfang: 8 S.
• Illustrationen: Diagramme
• Fussnoten: Gesehen am 22.07.2022
• Titel Quelle: Enthalten in: Anticancer research
• Ort Quelle: Attiki, 2004
• Jahr Quelle: 2011
• Band/Heft Quelle: 31(2011), 11 vom: Nov., Seite 3883-3890
• ISSN Quelle: 1791-7530
• Datenträger: Online-Ressource
• Sprache: eng
• Bibliogr. Hinweis: Erscheint auch als : Druck-Ausgabe: Correlation of gene expression of ATP-binding cassette protein and tyrosine kinase signaling pathway in patients with hepatocellular carcinoma. - 2011
• Sach-SW: ABC proteins
• Sach-SW: Hepatocellular carcinoma
• Sach-SW: liver resection
• Sach-SW: multidrug resistance
• Sach-SW: tyrosine kinase
• K10plus-PPN: 181143164X

Abstract

Background: Recent evidence suggests an involvement of the tyrosine kinase signaling pathway in the development of ATP-binding cassette (ABC) protein-mediated multidrug resistance in cancer. The aim of our study was to determine the relevance of kinase and multidrug-resistance protein expression in human hepatocellular carcinoma (HCC). Material and Methods: Paired tissue samples of HCC and corresponding peri-neoplastic tissue from 15 patients undergoing surgical resection were analyzed. The gene expression of ABC proteins and mitogen-activated protein kinase (MAPK) signaling cascade kinases was evaluated by real-time PCR and correlated with a series of clinicopathological parameters. In vitro effects of MAPK Kinase (MEK) inhibition were evaluated in HepG2 cells. Results: Overexpression of ABC proteins, tyrosine kinases, or both was detectable in 40%, 86% and 33% of HCC samples, respectively. ABCC1, -2 and -3-mRNA levels were significantly increased in 13%, 20% and 33% of the HCC samples compared to the corresponding peri-neoplastic tissue (p≤0.05). There was an association of ABCC1 and ABCC2 overexpression in HCC tissue (p≤0.05). EGFR, RAF, MEK, ERK and MAPK mRNA were overexpressed in 33%, 33%, 40%, 50% and 50%, respectively compared to the peri-neoplastic tissue (p≤0.05). The expression of ABCC1, ABCC2 and P-glycoprotein correlated statistically with the MEK gene expression. Patients with tyrosine kinase overexpression had significantly higher angioinvasion (p≤0.05). RAF overexpression correlated statistically with increased tumor size (p=0.052). In vitro, MEK inhibition led to a reduced ABCC1 mRNA and protein expression. Conclusion: ABC proteins and tyrosine kinases are significantly overexpressed in HCC tissue. The multidrug-resistance phenotype is associated with the MEK expression in HCC. Inhibition of MEK might be a new therapeutic approach to restore chemosensitivity in patients with highly resistant tumors.