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Wnt3a Growth Factor Induces Androgen Receptor-Mediated Transcription and Enhances Cell Growth in Human Prostate Cancer Cells

Departments of ¹ Urology, ² Genetics, and ³ Developmental Biology and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California

The Wnt signaling pathway plays a critical role in embryogenesis and tumorigenesis. However, biological roles of Wnt growth factors have not been fully characterized in prostate development and the pathogenesis of prostate cancer. In this study, we used Wnt3a-conditioned medium (Wnt3a-CM) and purified Wnt3a proteins to investigate whether there is a direct effect of Wnt3a on androgen receptor (AR)-mediated transcription and to determine its role in the growth of prostate cancer cells. We demonstrated that Wnt3a-CM either induces AR activity in the absence of androgens or enhances AR activity in the presence of low concentrations of androgens, whereas purified Wnt3a showed a pronounced effect in the presence of low concentrations of ligands. We also showed that Wnt3a-CM and the purified Wnt3a enhance the level of cytosolic and nuclear ß-catenin, suggesting an involvement of ß-catenin in this regulation. Moreover, treatment of LNCaP cells with Wnt3a-CM and purified Wnt3a significantly enhances cell growth in the absence of androgens. Our findings demonstrate that Wnt3a plays an important role in androgen-mediated transcription and cell growth. These results suggest a novel mechanism for the progression of prostate cancer.

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