Immunohistochemical analysis and mutational analyses of beta-catenin, Axin family and APC genes in hepatocellular carcinomas.
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.
Ishizaki
Yasuyo
Y
Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
Ikeda
Satoshi
S
Fujimori
Masahiko
M
Shimizu
Yosuke
Y
Kurihara
Takeshi
T
Itamoto
Toshiyuki
T
Kikuchi
Akira
A
Okajima
Masazumi
M
Asahara
Toshimasa
T
D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism; D000368:Aged; D060466:Axin Protein; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D051153:Wnt Proteins; D051176:beta Catenin
C555451:AXIN1 protein, human; C491761:AXIN2 protein, human; D025601:Adenomatous Polyposis Coli Protein; D060466:Axin Protein; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D051176:beta Catenin