Isolation and characterization of a novel human gene, DRCTNNB1A, the expression of which is down-regulated by beta-catenin

beta-Catenin plays significant roles in cell-to-cell adhesion and the Wnt/W g signal transduction pathway, Accumulation of this protein in the cytoplas m and nucleus as a result of mutations of the adenomatous polyposis coli tu mor suppressor gene or of the beta-catenin gene itself is often seen in a w ide variety of tumors including carcinomas of the colon, Liver, uterus, and brain. Interaction of accumulated beta-catenin with Tcf/Lef transcription factors is known to deregulate expression of some downstream genes, but the precise mechanisms whereby beta-catenin contributes to carcinogenesis rema in to be disclosed. Here we report isolation of a novel murine gene, Drctnn bla (down-regulated by Cfnnb1, a), the expression of which was experimental ly down-regulated in response to the activated form of beta-catenin. To inv estigate a possible role of DRCTNNB1A in cancers, we also isolated the huma n homologue, DRCTNNB1A, the deduced product of which was 91% identical to t he murine protein. The transcript was expressed in all human tissues examin ed, and we assigned the genomic location of DRCTNNB1A to chromosomal band 7 p15.3 by in situ hybridization. Expression of DRCTNNB1A in SW480 colon canc er cells was significantly increased in response to reduction of intracellu lar beta-catenin by adenovirus-mediated transfer of the beta-catenin-bindin g domain of the adenomatous polyposis coli gene into the cells. Furthermore , we documented reduced expression of DRCTNNB1A in 12 of 15 primary colorec tal cancers examined, compared with corresponding adjacent noncancerous muc osae, Our results implied that DRCTNNB1A is one of the genes involved in th e beta-catenin-Tcf/Lef signaling pathway, and that reduced expression of DR CTNNB1A may have some role in colorectal carcinogenesis.