Correlation of gene expression of ATP-binding cassette protein and tyrosine kinase signaling pathway in patients with hepatocellular carcinoma
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...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
[November 2011]
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| In: |
Anticancer research
Year: 2011, Volume: 31, Issue: 11, Pages: 3883-3890 |
| ISSN: | 1791-7530 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://ar.iiarjournals.org/content/31/11/3883
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| Author Notes: | Katrin Hoffmann, Lin Shibo, Zhi Xiao, Thomas Longerich, Markus W. Büchler and Peter Schemmer |
| Summary: | 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. |
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| Item Description: | Gesehen am 22.07.2022 |
| Physical Description: | Online Resource |
| ISSN: | 1791-7530 |