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肝细胞恶性转化过程中胰岛素样生长因子-I受体的动态表达与改变
Dynamic expression profile of the insulin-like growth factor-1 receptor during malignant transformation of hepatocytes
文章发布日期:2013年02月01日  来源:  作者:严晓娣,董志珍,陈 洁,等  点击次数:2715次  下载次数:654次

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【摘要】:目的观察肝细胞恶性转化过程中胰岛素样生长因子-I受体(IGF-IR)的动态表达与改变特征。方法以2-乙酰氨基芴(2-FAA)喂饲雄性SD大鼠诱发肝癌发生,分别观察肝细胞形态学、肝及血IGF-1R的动态变化。以免疫组化法观察肝组织IGF-1R表达,以RT-PCR扩增IGF-1R mRNA表达片段并经测序证实,从基因转录和蛋白水平上分析与肝细胞恶性转化的相互关系。结果诱癌过程中肝细胞出现颗粒样变性、癌前病变到肝癌形成的动态变化,伴肝核酸代谢旺盛,肝IGF-IR表达异常;肝IGF-IR阳性率(%)、肝IGF-IR mRNA阳性率(%)、肝IGF-IR比浓度(ng/mg肝组织)和血IGF-IR(ng/ml)分别为:对照组0、0、0.63±0.17和1.33±0.47;变性组50、61.1、0.65±0.2和1.51±0.46;癌前组88.9、100、0.66±0.14和1.92±0.29;癌变组100、100、0.96±0.09和2.43±0.57。IGF-IR在转录或蛋白水平上呈梯度表达,癌变组显著高于其他组(P<0.01),且肝和血IGF-IR呈显著正相关(r=0.91,t=14.222, P<0.001)。结论IGF-1R过表达参与肝细胞癌变,是肝细胞恶性转化的早期标志。
【Abstract】:Objective To determine the dynamic expression pattern and investigate the mechanisms underlying modified expression of insulin-like growth factor-1 receptor (IGF-1R) during malignant transformation of hepatocytes. MethodsThe N-2-fluorenylacetamide-induced liver cancer model was established in male Sprague-Dawley rats. Uninduced rats served as controls. Morphological changes were observed in livers by histological analysis. Dynamic changes in liver and serum expression of IGF-1R were analyzed and quantitated by immunohistochemistry, immunoassays, and RT-PCR with DNA sequencing. The relation between IGF-1R expression and malignant transformation of hepatocytes was investigated at both the gene transcription and protein expression levels using rank correlation analysis. ResultsThe 2-FAA-induced rat hepatocytes showed remarkable morphologic alterations, including granule-like degeneration and other features of precancerous to hepatoma formation, which paralleled with increases in IGF-1R expression. Comparison of the control rats, precancerous rats, degenerated rats, and hepatoma rats indicated differential profiles of liver IGF-IR (0, 88.9%, 50.0%, and 100%), IGF-IR mRNA (0, 100%, 61.1%, and 100 %), specific IGF-IR concentration (0.63±0.17, 0.66±0.14, 0.65±0.2, and 0.96±0.09, ng/mg wet liver), and serum IGF-IR level (1.33±0.47, 1.92±0.29, 1.51±0.46, and 2.43±0.57 ng/ml). The serum IGF-1R expression was significantly higher in the hepatoma group than in any of other groups (gene transcription and protein levels, P<0.01). A positive relationship was found between liver and sera levels of IGF-1R (r=0.91, t=14.222, P<0.01). ConclusionIGF-1R may participate in hepatocyte canceration. Overexpression of IGF-1R may represent a useful early marker to identify and monitor malignant transformation of hepatocytes.
【关键字】:癌,肝细胞;受体,IGF1型;基因扩增;序列分析,RNA
【Key words】:carcinoma, hepatocellular; receptor, IGF type 1; gene amplification; sequence analysis, RNA
【引证本文】:

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