Ueno T, Hashimoto O, Kimura R, Torimura T, Kawaguchi T, Nakamura T, Sakata R, Koga H, Sata M
Kurume University Research Center for Innovative Cancer Therapy, Second Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
Int J Oncol. 2001 Jan;18(1):49-55. doi: 10.3892/ijo.18.1.49.
Hepatocarcinogenesis is closely related to hepatic fibrosis. In this study, we investigated the relationship of type II transforming growth factor-beta receptor (T beta RII) to hepatic fibrosis and hepatocellular carcinoma (HCC). In vivo: liver tissues were obtained from 30 patients (10 chronic hepatitis, 7 cirrhosis, 13 HCC). Protein expression and immunolocalization of T beta RII were examined by Western blot analysis and immunohistochemistry. In vitro: T beta RII protein expression in hepatoma cell lines (HepG2, Hep3B, HLE, HLF and Huh7) was examined by Western blot analysis. Next, we transfected T beta RII cDNA to Huh7, and compared the change of cell number and observed the induction of apoptosis after TGF-beta1 treatment using a FACScan flow cytometer. In vivo: T beta RII immunolocalization in liver tissues was significantly decreased in patients with HCC compared with that of patients with chronic hepatitis or liver cirrhosis. In Western blot analysis, T beta RII expression in tissues attenuated in comparison with that in non-tumor tissues in some patients with HCC. In vitro: T beta RII protein expression in HLE, HLF and Huh7 cells was weaker than that in HepG2 and Hep3B cells. In Huh7 cells transfected T beta RII cDNA, cell arrest and apoptosis were obviously induced. These results indicated that human HCC has a reduced expression of T beta RII for TGF-beta1. This may provide a selective growth advantage to HCC to escape the inhibitory growth signals of TGF-beta1, and may be linked with critical steps in the growth of hepatoma cells.
肝癌发生与肝纤维化密切相关。在本研究中，我们调查了II型转化生长因子-β受体（TβRII）与肝纤维化和肝细胞癌（HCC）的关系。体内实验：从30例患者（10例慢性肝炎、7例肝硬化、13例HCC）获取肝组织。通过蛋白质印迹分析和免疫组织化学检测TβRII的蛋白表达和免疫定位。体外实验：通过蛋白质印迹分析检测肝癌细胞系（HepG2、Hep3B、HLE、HLF和Huh7）中TβRII蛋白表达。接下来，我们将TβRII cDNA转染至Huh7，并使用FACScan流式细胞仪比较细胞数量变化并观察TGF-β1处理后凋亡的诱导情况。体内实验：与慢性肝炎或肝硬化患者相比，HCC患者肝组织中TβRII免疫定位显著降低。在蛋白质印迹分析中，一些HCC患者组织中TβRII表达与非肿瘤组织相比减弱。体外实验：HLE、HLF和Huh7细胞中TβRII蛋白表达弱于HepG2和Hep3B细胞。在转染TβRII cDNA的Huh7细胞中，明显诱导了细胞停滞和凋亡。这些结果表明，人类HCC中TβRII对TGF-β1的表达降低。这可能为HCC提供选择性生长优势以逃避TGF-β1的生长抑制信号，并且可能与肝癌细胞生长的关键步骤有关。
