Basic-alimentary tractβ-Catenin Interacts With the FUS Proto-oncogene Product and Regulates Pre-mRNA Splicing
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Cell Lines
Human embryonic kidney (HEK) cell line 293 and human colorectal cancer cell lines DLD-1, RCM-1, LoVo, COLO320, CCK-81, SW837, and COLO201 were obtained from the Health Science Research Resources Bank (Osaka, Japan). Human cervical cancer cell line HeLa, human breast cancer cell lines MCF-7 and MDA-MB-435, and simian kidney epithelial cell line Cos-7 were purchased from the Riken Cell Bank (Tsukuba, Japan). Human colorectal cancer cell lines SW48, LS174T, HT-29, SW1116, HCT-8, HCT-116, SW403,
Assembly of β-Catenin-Containing Nuclear Complex in a Colorectal Cancer Cell Line
At least 12 proteins in addition to β-catenin were constantly immunoprecipitated by the anti-β-catenin antibody, but not by normal control mouse IgG, from nuclear extracts obtained from a colorectal adenocarcinoma cell line, DLD-1 (Figure 1A). DLD-1 cells accumulate β-catenin protein as a result of a truncational mutation and loss of heterozygosity (LOH) in the APC genes.5 Mass spectrometric analysis revealed that these proteins included DNA topoisomerase IIα (TOP2A), DEAD-box RNA helicases
Discussion
In this study, we demonstrated the physical interaction of a protooncogene product, β-catenin, with another protooncogene product, FUS (Figure 1, Figure 2, Figure 3). The expression level of FUS protein decreased gradually from the bottom to the surface of the intestinal crypts (Figure 4A–D). The expression pattern of FUS in the adenoma cells completely paralleled that of accumulated β-catenin protein (Figure 4E–H). The FUS protein was strongly expressed in the nuclei of adenocarcinoma cells
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Supported by a grant from the Ministry of Health, Labor, and Welfare and by the “Program for Promotion of Fundamental Studies in Health Sciences” of the National Institute of Biological Innovation of Japan.