1. The β-Catenin/T-Cell Factor/Lymphocyte Enhancer Factor Signaling Pathway Is Required for Normal and Stress-Induced Cardiac Hypertrophy.
- Author
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Xin Chen, Shevtsov, Sergei P., Hsich, Eileen, Lei Cui, Syed Haq, Aronovitz, Mark, Kerkelä, Risto, Molkentin, Jeffery D., Liao, Ronglih, Salomon, Robert N., Patten, Richard, and Force, Thomas
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CELL cycle , *TRANSCRIPTION factors , *HEART disease genetics , *HYPERTROPHY , *CELLS - Abstract
In cells capable of entering the cell cycle, including cancer cells, β-catenin has been termed a master switch, driving proliferation over differentiation. However, its role as a transcriptional activator in terminally differentiated cells is relatively unknown. Herein we utilize conditional, cardiac-specific deletion of the β-catenin gene and cardiac-specific expression of a dominant inhibitory mutant of Lef-1 (Lef-1Δ20), one of the members of the T-cell factor/lymphocyte enhancer factor (Tcf/Lef) family of transcription factors that functions as a coactivator with β-catenin, to demonstrate that β-catenin/Tcf/Lef-dependent gene expression regulates both physiologic and pathological growth (hypertrophy) of the heart. Indeed, the profound nature of the growth impairment of the heart in the Lef-1Δ20 mouse, which leads to very early development of heart failure and premature death, suggests β-catenin/Tcf/Lef targets are dominant regulators of cardiomyocyte growth. Thus, our studies, employing complementary models in vivo, implicate β-catenin/Tcf/Lef signaling as an essential growth-regulatory pathway in terminally differentiated cells. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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