Identification of T-cell factor-4 isoforms that contribute to the malignant phenotype of XXXX cells.

@entity5907 @entity1 @entity1522 @entity157 @entity15914
The Wnt/b-catenin signaling pathway is frequently activated in @entity157 ( @entity157 ). Downstream signaling events involving the Wnt/b-catenin cascade occur through @entity5907 ( @entity5907 ) proteins. The @entity1 @entity15914 gene is composed of 17 exons with multiple alternative splicing sites. However, the role of different @entity15914 isoforms in the pathogenesis of @entity157 is unknown. The purpose of this study was to identify and characterize @entity15914 isoforms in @entity157 . We identified 14 novel @entity15914 isoforms from four @entity157 cell lines. Functional analysis following transfection and expression in @entity157 cells revealed distinct effects on the phenotype. The @entity15914 J isoform expression produced striking features of malignant transformation characterized by high cell proliferation rate, migration and colony formation even though its transcriptional activity was low. In contrast, the @entity5907 -4K isoform displayed low @entity5907 transcriptional activity; cell proliferation rate and colony formation were reduced as well. Interestingly, @entity5907 -4J and @entity15914 K differed by only five @entity1522 (the SxxSS motif). Thus, these studies suggest that conserved splicing motifs may have a major influence on the transcriptional activity and functional properties of @entity15914 isoforms and alter the characteristics of the malignant phenotype.
