Mutational Analysis of the APC/β-Catenin/Tcf Pathway in Colorectal Cancer
作者： Bert Vogelstein , Kenneth W. Kinzler , Patrice J. Morin , Andrew B. Sparks
DOI:
关键词: Immunology 、 Medicine 、 Colorectal cancer 、 Carcinogenesis 、 Adenomatous polyposis coli 、 Tumor progression 、 Cancer research 、 Catenin 、 Gene 、 Tumor suppressor gene 、 Transactivation
摘要: Abstract Mutation of the adenomatous polyposis coli ( APC ) tumor suppressor gene initiates majority colorectal (CR) cancers. One consequence this inactivation is constitutive activation β-catenin/Tcf-mediated transcription. To further explore role APC/β-catenin/Tcf pathway in CR tumorigenesis, we searched for mutations genes implicated tumors lacking mutations. No γ-catenin CTNNG1 ), GSK-3α GSK3A or GSK-3β GSK3B were detected. In contrast, NH 2 -terminal regulatory domain β-catenin CTNNB1 found 13 27 (48%) Mutations and observed to be mutually exclusive, consistent with their equivalent effects on stability Tcf transactivation. addition, that can occur early, stage neoplasia, as has been previously These results suggest uniquely substitute signaling plays a critical tumorigenesis.
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