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Activation of Signal Transducer and Activator of Transcription 5 is Required for Progression of Autochthonous Prostate Cancer

Evidence from the Transgenic Adenocarcinoma of the Mouse Prostate System

¹ Departments of Molecular and Cellular Biology and
² Immunology and
³ Scott Department of Urology, Baylor College of Medicine, Houston, Texas

The constitutive activation of signal transducer and activator of transcription (STAT) proteins has been demonstrated in many diverse human cancer cell lines and clinical tumors including prostate cancer. The STAT family has at least seven members, and the two forms of the STAT5 protein, STAT5A and STAT5B, exhibit a high degree of sequence similarity. We have reported previously that expression of STAT5B, but not STAT5A, could enhance the transforming potential of v-src and induces cell cycle progression and motility in fibroblasts. In the current study we demonstrate specific activation of STAT5B in epithelial cells representing invasive and metastatic prostate cancer. We also demonstrate that the naturally occurring dominant-negative isoform STAT5B can block cell cycle progression through G₁ and inhibit the growth, invasive potential, and clonogenic ability of these prostate cancer cell lines. Furthermore, we report that the dominant-negative isoform STAT5B can inhibit the growth of prostate cancer cells in grafting studies. These results support our hypothesis that specific activation of STAT5, in particular STAT5B, facilitates the progression of prostate cancer.

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