Infrequent somatic mutations of the ICAT gene in various human cancers with frequent 1p-LOH and/or abnormal nuclear accumulation of beta-catenin.
Abnormal nuclear accumulation of beta-catenin (CTNNB1) plays one of the key roles in the upregulation of the Wnt signalling pathway that can cause acceleration of cell proliferation. ICAT, inhibitor of beta-catenin and TCF4/beta-catenin-interacting protein, was isolated and mapped to 1p36, a frequent target for LOH in many human cancers. We have previously observed that a number of tumors showing abnormal accumulation of the CTNNB1 protein do not harbor a mutation of the CTNNB1 gene. We studied the precise localization and genomic structure of the ICAT gene and analyzed its mutations in 178 human tumors developed in organs with frequent nuclear accumulation of the CTNNB1 protein and/or frequent LOHs of 1p36, but no genetic alterations were observed. Our results imply that i) genetic alteration of the ICAT gene does not play an important role in abnormal accumulation of CTNNB1 that would cause up-regulation of the Wnt signalling pathway, ii) mechanisms other than genetic alteration may have inactivated ICAT function, or iii) gene(s) on 1p36 other than ICAT may be the responsible tumor suppressor gene for tumors that show frequent 1p36-LOH.
Imai
Mitsuho
M
Department of Molecular Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Nakamura
Tsutomu
T
Akiyama
Tetsu
T
Horii
Akira
A
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins / Q000235:genetics*; D002467:Cell Nucleus; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019656:Loss of Heterozygosity / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012097:Repressor Proteins / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D014407:Tumor Cells, Cultured; D051176:beta Catenin
D048868:Adaptor Proteins, Signal Transducing; C495270:CTNNB1 protein, human; C411982:CTNNBIP1 protein, human; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D051176:beta Catenin