Role of a BCL9-related beta-catenin-binding protein, B9L, in tumorigenesis induced by aberrant activation of Wnt signaling.

Wnt signaling plays a crucial role in a number of developmental processes and in tumorigenesis. beta-Catenin is stabilized by Wnt signaling and associates with the TCF/LEF family of transcription factors, thereby activating transcription of Wnt target genes. Constitutive activation of beta-catenin-TCF-mediated transcription resulting from mutations in adenomatous polyposis coli (APC), ...
beta-catenin, or Axin is believed to be a critical step in tumorigenesis among divergent types of cancers. Here we show that the transactivation potential of the beta-catenin-TCF complex is enhanced by its interaction with a BCL9-like protein, B9L, in addition to BCL9. We found that B9L is required for enhanced beta-catenin-TCF-mediated transcription in colorectal tumor cells and for beta-catenin-induced transformation of RK3E cells. Furthermore, expression of B9L was aberrantly elevated in about 43% of colorectal tumors, relative to the corresponding noncancerous tissues. These results suggest that B9L plays an important role in tumorigenesis induced by aberrant activation of Wnt signaling.
Mesh Terms:
Amino Acid Sequence, Animals, Cell Transformation, Neoplastic, Colorectal Neoplasms, Cytoskeletal Proteins, DNA-Binding Proteins, Humans, Immunohistochemistry, Intercellular Signaling Peptides and Proteins, Lymphoid Enhancer-Binding Factor 1, Molecular Sequence Data, Protein Binding, Rats, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Trans-Activators, Transcription Factors, Transcription, Genetic, Transfection, Wnt Proteins, beta Catenin
Cancer Res.
Date: Dec. 01, 2004
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