Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Hoffmann, K; Shibo, L; Xiao, Z; Longerich, T; Büchler, MW; Schemmer, P.
Correlation of gene expression of ATP-binding cassette protein and tyrosine kinase signaling pathway in patients with hepatocellular carcinoma.
Anticancer Res. 2011; 31(11):3883-3890
Web of Science
PubMed
- Leading authors Med Uni Graz
- Schemmer Peter
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- Abstract:
- 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). 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. 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. 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Aged -
- Carcinoma, Hepatocellular - genetics
- Carcinoma, Hepatocellular - metabolism
- Carcinoma, Hepatocellular - pathology
- Drug Resistance, Neoplasm -
- Female -
- Humans -
- Liver Neoplasms - genetics
- Liver Neoplasms - metabolism
- Liver Neoplasms - pathology
- Male -
- Middle Aged -
- Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors
- Mitogen-Activated Protein Kinase Kinases - genetics
- Mitogen-Activated Protein Kinase Kinases - metabolism
- Mitogen-Activated Protein Kinases - genetics
- Mitogen-Activated Protein Kinases - metabolism
- Neoplasm Grading -
- Neoplasm Staging -
- P-Glycoproteins - genetics
- P-Glycoproteins - metabolism
- Prognosis -
- Protein-Tyrosine Kinases - genetics
- Protein-Tyrosine Kinases - metabolism
- RNA, Messenger - genetics
- RNA, Small Interfering - genetics
- Real-Time Polymerase Chain Reaction -
- Signal Transduction -
- Tumor Cells, Cultured -
- raf Kinases - genetics
- raf Kinases - metabolism
- Find related publications in this database (Keywords)
- Hepatocellular carcinoma
- liver resection
- multidrug resistance
- ABC proteins
- tyrosine kinase