Ishizaki Yasuyo, Ikeda Satoshi, Fujimori Masahiko, Shimizu Yosuke, Kurihara Takeshi, Itamoto Toshiyuki, Kikuchi Akira, Okajima Masazumi, Asahara Toshimasa
Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
Int J Oncol. 2004 May;24(5):1077-83.
Several lines of evidence show that the development of hepatocellular carcinoma (HCC) requires an accumulation of genetic alterations. However, molecular mechanism in HCC carcinogenesis remains unsolved. A total of 89 HCC samples were analyzed in this study to determine how alterations in the Wnt signaling pathway associate with the carcinogenesis of HCC. beta-catenin immunohistochemistry showed positive nuclear staining in 24 (27.0%) of the 89 HCC samples, indicating the existence of alterations in the Wnt signaling pathway in those 24 HCC samples. Mutations in the beta-catenin, Axin1 and Axin2 genes were detected in 10 (41.7%), 13 (54.2%) and 9 (37.5%) of the 24 beta-catenin-positive samples, respectively, but no mutation was detected in the APC gene. In conclusion, in addition to mutations in the beta-catenin gene, mutations in the Axin1 and Axin2 genes may alter the Wnt signaling pathway, resulting in accumulation of beta-catenin.
多项证据表明，肝细胞癌（HCC）的发生需要基因改变的积累。然而，HCC致癌的分子机制仍未解决。本研究共分析了89例HCC样本，以确定Wnt信号通路的改变与HCC致癌作用之间的关联。β-连环蛋白免疫组化显示，89例HCC样本中有24例（27.0%）核染色呈阳性，表明这24例HCC样本中存在Wnt信号通路的改变。在24例β-连环蛋白阳性样本中，分别有10例（41.7%）、13例（54.2%）和9例（37.5%）检测到β-连环蛋白、Axin1和Axin2基因的突变，但未在APC基因中检测到突变。总之，除了β-连环蛋白基因的突变外，Axin1和Axin2基因的突变可能会改变Wnt信号通路，导致β-连环蛋白的积累。
