Expression profiles of βTRCP1 and βTRCP2, and mutation analysis of βTRCP2 in gastric cancer

βTRCP1 and βTRCP2, components of the β-catenin-ubiquitin ligase complex, are negative regulators of the WNT signaling pathway. We have previously isolated the βTRCP2 gene, and detected βTRCP2 in all gastric cancer cell lines examined. Here, expression profiles of βTRCP1 and βTRCP2 in various normal tissues and in primary gastric cancer were investigated. βTRCP1 was predominant in small intestine, while βTRCP2 was predominant in stomach. βTRCP1 was expressed in gastric cancer cell lines MKN28, MKN45, MKN74, and KATO-III, but not in any cases of primary gastric cancer. βTRCP2 was expressed in most cases of primary gastric cancer at almost the equal level in tumor and in non-cancerous portion of gastric mucosa. As βTRCP2 was found to be the major βTRCP expressed in gastric cancer, genetic alterations of βTRCP2 in 7 gastric cancer cell lines and 12 cases of primary gastric cancer were investigated. A nucleotide substitution (T↷C) at the nucleotide position 1486 of βTRCP2 was identified in OKAJIMA cells, which lead to F462S amino acid substitution in the seventh WD-repeat domain. F462 was conserved among βTRCPs derived from human, mouse, Xenopus laevis, and Drosophila melanogaster. As WD-repeats of βTRCPs are the substrate-recognition motif of the β-catenin-ubiquitin ligase, F462S amino-acid substitution might lead to β-catenin stabilization, and might be implicated in carcinogenesis through activation of the WNT signaling pathway. This is the first report on comprehensive expression analyses of βTRCP1 and βTRCP2, and also on mutation analysis of βTRCP2.