Identification of T-cell factor-4 isoforms that contribute to the malignant phenotype of hepatocellular carcinoma cells

Journal Article · Fri Apr 15 00:00:00 EDT 2011 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2011.01.015· OSTI ID:22212110

Tsedensodnom, Orkhontuya ^[1]; Koga, Hironori; Rosenberg, Stephen A.; Nambotin, Sarah B.; Carroll, John J.; Wands, Jack R. ^[1]; Kim, Miran ^[1]

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1. Liver Research Center, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI (United States)

The Wnt/{beta}-catenin signaling pathway is frequently activated in hepatocellular carcinoma (HCC). Downstream signaling events involving the Wnt/{beta}-catenin cascade occur through T-cell factor (TCF) proteins. The human TCF-4 gene is composed of 17 exons with multiple alternative splicing sites. However, the role of different TCF-4 isoforms in the pathogenesis of HCC is unknown. The purpose of this study was to identify and characterize TCF-4 isoforms in HCC. We identified 14 novel TCF-4 isoforms from four HCC cell lines. Functional analysis following transfection and expression in HCC cells revealed distinct effects on the phenotype. The TCF-4J 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 TCF-4K isoform displayed low TCF transcriptional activity; cell proliferation rate and colony formation were reduced as well. Interestingly, TCF-4J and TCF-4K differed by only five amino acids (the SxxSS motif). Thus, these studies suggest that conserved splicing motifs may have a major influence on the transcriptional activity and functional properties of TCF-4 isoforms and alter the characteristics of the malignant phenotype.

• OSTI ID: 22212110
• Journal Information: Experimental Cell Research, Vol. 317, Issue 7; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMINO ACIDS
CELL PROLIFERATION
COLONY FORMATION
FUNCTIONAL ANALYSIS
HEPATOMAS
PATHOGENESIS
PHENOTYPE
RECEPTORS
SPLICING
TRANSCRIPTION