β-Catenin plays a key role in metastasis of human hepatocellular carcinoma

Abstract

Currently, there are no diagnostic or metastatic markers that can be used in early diagnosis and treatment of human hepatocellular carcinoma (HCC). The aim of this study was to find a molecular marker that regulated migration and metastasis in HCC. We analyzed the gene expression of β-catenin, c-Myc and IL-8 in human HCC tissue by RT-PCR and immunohistochemistry and analyzed five variously differentiated HCC cell lines by Western blotting and migration and invasion assays to find markers for HCC diagnosis and HCC metastasis. mRNA expression of β-catenin was significantly higher in the tumor area compared to the nontumor area and was more abundant in specimens of late-stage HCC. Immunohi stochemistry revealed that the translocation of β-catenin into the nucleus was closely correlated with IL-8 protein levels and tumor stage. Similarly, the level of expression and nuclear translocation of β-catenin was greater in HA22T cells with high proliferative activity than in HCC cell lines with low proliferative activity (PLC, Hep3B, HepG2). Knockdown of the β-catenin gene with β-catenin antisense oligonucleotides resulted in inhibition of cell migration and invasion of HA22T cells. Taken together, these results suggest that β-catenin may be a suitable diagnostic marker of metastasis in human HCC.