School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C.
Oncol Rep. 2011 Aug;26(2):415-22. doi: 10.3892/or.2011.1323. Epub 2011 May 26.
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 non-tumor area and was more abundant in specimens of late-stage HCC. Immunohistochemistry 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.
目前,尚无可用于人肝癌(HCC)早期诊断和治疗的诊断或转移标志物。本研究旨在寻找调节 HCC 迁移和转移的分子标志物。我们通过 RT-PCR 和免疫组织化学分析了人 HCC 组织中β-catenin、c-Myc 和 IL-8 的基因表达,并通过 Western blot 和迁移侵袭实验分析了五种不同分化的 HCC 细胞系,以寻找 HCC 诊断和 HCC 转移的标志物。β-catenin 的 mRNA 表达在肿瘤区域明显高于非肿瘤区域,在晚期 HCC 标本中更为丰富。免疫组织化学显示β-catenin 向核内易位与 IL-8 蛋白水平和肿瘤分期密切相关。同样,具有高增殖活性的 HA22T 细胞中β-catenin 的表达水平和核易位高于增殖活性低的 HCC 细胞系(PLC、Hep3B、HepG2)。用β-catenin 反义寡核苷酸敲低β-catenin 基因可抑制 HA22T 细胞的迁移和侵袭。总之,这些结果表明β-catenin 可能是人类 HCC 转移的合适诊断标志物。