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ß-Catenin Is Involved in Insulin-Like Growth Factor 1-Mediated Transactivation of the Androgen Receptor

Department of Urology and Department of Genetics, Stanford University School of Medicine, Stanford, California 94305-5328

Address all correspondence and requests for reprints to: Dr. Zijie Sun, Department of Urology and Department of Genetics, R135, Edwards Building, Stanford University School of Medicine, Stanford, California 94305-5328. E-mail: zsun{at}stanford.edu.

The androgen-signaling pathway is important for the growth and progression of prostate cancer cells. IGF-I and other polypeptide growth factors have been shown to be capable of induction of androgen receptor (AR) activation in the absence of, or at low levels of, ligand. It has been shown that IGF-I increases the cellular level of ß-catenin, an AR coactivator. In this study, we performed several experiments to test whether ß-catenin is involved in IGF-I-induced AR-mediated transcription. We demonstrate that IGF-I enhances the expression of endogenous prostate-specific antigen, an AR target gene, and elevates the level of cytoplasmic and nuclear ß-catenin in prostate cancer cells. Transfection of either wild-type or a constitutively active mutant of the IGF-I receptor augments AR-mediated transcription. An antisense construct of ß-catenin that decreases the cellular level of ß-catenin can reduce IGF-1 receptor-mediated enhancement of AR activity. Moreover, using a pulse-chase experiment, we showed that IGF-I enhances the stability of ß-catenin in prostate cancer cells. Our findings delineate a novel pathway for IGF-I in modulating androgen signaling through ß-catenin.

NURSA Molecule Pages Link:

Nuclear Receptors:   AR

Ligands:   Dihydrotestosterone

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