β-Catenin expression and mutational analysis in renal cell carcinomas

Young Sik Kim, Yong Koo Kang, Jung Bun Kim, Seon Ae Han, Kwang Kim, Seung R. Paik

    Research output: Contribution to journalArticlepeer-review

    45 Citations (Scopus)

    Abstract

    β-Catenin acts as a downstream transcriptional activator of the Wingless-Wnt signaling pathway. The β-catenin-Tcf complex transactivates the downstream genes that regulate cell proliferation or inhibit apoptosis. The activation of this pathway through stabilization of β-catenin is caused either by inactivating mutations of adenomatous polyposis coli (APC) tumor suppressor gene or by activating mutations in β-catenin exon 3. To determine whether the abnormal expression and activating mutations in exon 3 of the β-catenin gene are implicated in renal cell carcinogenesis, 52 renal cell carcinomas (RCC) were analyzed by immunohistochemistry, polymerase chain reaction-single-strand conformational polymorphism analysis (PCR-SSCP), and direct DNA sequencing. Immunohistochemically, all cases, as well as normal kidneys, showed membranous and/or cytoplasmic staining patterns without nuclear localization. However, the cytoplasmic accumulations of β-catenin were observed in five (22.7%) of 22 cases of conventional (clear cell) renal carcinoma, but not in papillary or chromophobe renal carcinomas. The β-catenin mutation was identified in only one case of conventional renal carcinoma and was a single-base missense mutation on codon 61, leading to substitution of glutamine by arginine. In conclusion, this study demonstrates that β-catenin mutations are a relatively rare event in RCC and that cytoplasmic accumulations of β-catenin protein are found only in conventional (clear cell) renal carcinomas. These data suggest that the activation of the β-catenin signaling pathway may partly play a role in the development of conventional RCC.

    Original languageEnglish
    Pages (from-to)725-730
    Number of pages6
    JournalPathology International
    Volume50
    Issue number9
    DOIs
    Publication statusPublished - 2000

    Keywords

    • Mutation
    • Renal cell carcinoma
    • β-catenin

    ASJC Scopus subject areas

    • Pathology and Forensic Medicine

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