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/Wg signal transduction pathway. Accumulation of this protein in the cytoplasm and nucleus as a result of mutations of the adenomatous polyposis coli tumor suppressor gene or of the beta-catenin gene itself is often seen in a wide 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 remain to be disclosed. Here we report isolation of a novel murine gene, Drctnnb1a (down-regulated by Ctnnb1, a), the expression of which was experimentally down-regulated in response to the activated form of beta-catenin. To investigate a possible role of DRCTNNB1A in cancers, we also isolated the human homologue, DRCTNNB1A, the deduced product of which was 91% identical to the murine protein. The transcript was expressed in all human tissues examined, and we assigned the genomic location of DRCTNNB1A to chromosomal band 7p15.3 by in situ hybridization. Expression of DRCTNNB1A in SW480 colon cancer cells was significantly increased in response to reduction of intracellular beta-catenin by adenovirus-mediated transfer of the beta-catenin-binding domain of the adenomatous polyposis coli gene into the cells. Furthermore, we documented reduced expression of DRCTNNB1A in 12 of 15 primary colorectal cancers examined, compared with corresponding adjacent noncancerous mucosae. Our results implied that DRCTNNB1A is one of the genes involved in the beta-catenin-Tcf/Lef signaling pathway, and that reduced expression of DRCTNNB1A may have some role in colorectal carcinogenesis.
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Japan.
T
T
Kawasoe
Y
Y
Furukawa
Y
Y
Daigo
T
T
Nishiwaki
H
H
Ishiguro
M
M
Fujita
S
S
Satoh
N
N
Miwa
Y
Y
Nagasawa
Y
Y
Miyoshi
M
M
Ogawa
Y
Y
Nakamura
D000818:Animals; D019556:COS Cells; D015820:Cadherins / Q000235:genetics / Q000502:physiology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007739:L Cells; D008565:Membrane Proteins; D051379:Mice; D015513:Oncogene Proteins / Q000235:genetics*; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015534:Trans-Activators; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D051176:beta Catenin
D015820:Cadherins; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D015513:Oncogene Proteins; D011994:Recombinant Proteins; D015534:Trans-Activators; D051176:beta Catenin; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; C485859:Drctnnb1a protein, mouse; C412048:HYCC1 protein, human