Cui J, Zhou X, Liu Y, Tang Z
Department of Food Science and Human Nutrition, Michigan State University, East Lansing 48824, USA.
J Cancer Res Clin Oncol. 2001 Sep;127(9):577-81. doi: 10.1007/s004320100259.
To study the role of beta-catenin gene mutation and expression in hepatocellular carcinogenesis.
Thirty-four hepatocellular carcinoma (HCC) specimens and adjacent para-cancerous tissues, and four normal liver tissues were analyzed. Subcellular distribution of beta-catenin was examined by immunohistochemistry staining. Mutation and semiquantitative expression of beta-catenin gene exon 3 mRNA were detected by RT-PCR-SSCP and in situ hybridization.
Immunohistochemistry showed that all normal liver tissues and para-cancerous tissues examined showed membranous-type staining for beta-catenin protein, frequently with weak expression in the cytoplasm, but no beta-catenin accumulation in nuclei was found; while in liver cancer, 21 cases (61.8%) of HCC examined showed accumulated type in cytoplasms or nuclei. On SSCP, 15 cases (44.1%) of HCC altogether displayed three kinds of characteristic mutational mobility shifts. No abnormal shifting bands were found in tissues from normal liver or para-cancerous area. The beta-catenin gene exon 3 mRNA expression index of 34 HCCs was higher than that of para-cancerous tissue and normal liver tissue. Using in situ hybridization, the signal corresponding to beta-catenin gene exon 3 mRNA was particularly strong in cytoplasm of HCC when compared with those of paracancerous tissues and normal liver tissues.
beta-catenin gene mutation and overexpression may have a critical role in malignant progression of hepatic carcinogenesis among Chinese people.
研究β-连环蛋白基因突变及表达在肝细胞癌发生中的作用。
分析34例肝细胞癌(HCC)标本及其癌旁组织,以及4例正常肝组织。采用免疫组织化学染色检测β-连环蛋白的亚细胞分布。通过逆转录聚合酶链反应-单链构象多态性(RT-PCR-SSCP)和原位杂交检测β-连环蛋白基因外显子3 mRNA的突变及半定量表达。
免疫组织化学显示,所有检测的正常肝组织和癌旁组织中β-连环蛋白蛋白呈膜型染色,细胞质中常呈弱表达,但细胞核内未发现β-连环蛋白积聚;而在肝癌中,21例(61.8%)检测的HCC显示细胞质或细胞核中有积聚型。在SSCP上,共15例(44.1%)HCC出现三种特征性的突变迁移率改变。正常肝组织或癌旁组织中未发现异常迁移条带。34例HCC的β-连环蛋白基因外显子3 mRNA表达指数高于癌旁组织和正常肝组织。采用原位杂交,与癌旁组织和正常肝组织相比,HCC细胞质中对应β-连环蛋白基因外显子3 mRNA的信号特别强。
β-连环蛋白基因突变和过表达可能在中国人群肝癌发生的恶性进展中起关键作用。