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

摘要

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