title: Beta-catenin mutations in human prostate cancer.
abstract: Beta-catenin plays essential roles in both intercellular adhesion and signal transduction. As a signaling molecule, beta-catenin supplies an activating domain to the T-cell factor/lymphoid enhancer-binding factor family of DNA-binding proteins and activates gene transcription. Posttranslational stabilization of beta-catenin, leading to elevated protein levels and constitutive gene activation, has been proposed as an important step in oncogenesis. Stabilization of beta-catenin can occur through mutation to highly conserved amino acids encoded in exon 3 of the beta-catenin gene (CTNNB1). To determine whether this pathway of malignant transformation is important in prostate cancer, we analyzed 104 prostate cancer tissue specimens, 4 prostate cancer cell lines, and 3 prostate tumor xenografts for activating mutations in exon 3 of CTNNB1. Mutations were detected in 5 of the 104 prostate cancer tissue samples. Four of the five mutations involved serine or threonine residues implicated in the degradation of beta-catenin. A fifth tumor had a mutation at codon 32, changing a highly conserved aspartic acid to a tyrosine. Mutational analysis of multiple regions from several tumor samples showed that the beta-catenin mutations were present focally and therefore may occur during tumor progression.
authors.affiliation: Division of Hematology/Oncology, Lombardi Cancer Center, Georgetown University School of Medicine, Washington, DC 20007-2197, USA.
authors.forename: H J
authors.initials: HJ
authors.lastname: Voeller
authors.forename: C I
authors.initials: CI
authors.lastname: Truica
authors.forename: E P
authors.initials: EP
authors.lastname: Gelmann
mesh_terms: D003598:Cytoskeletal Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000235:genetics*; D015534:Trans-Activators; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins; D015534:Trans-Activators; D051176:beta Catenin