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Departments of Biochemistry and Molecular Biology and Urology, Mayo Clinic, Rochester, Minnesota 55905
Prostate cancer cells depend on androgens and the androgen receptor (AR) for survival. However, after androgen ablation therapy, tumors relapse to an androgen-refractory state. To determine whether the androgen receptor is critical for proliferation of androgen-refractory prostate cancer cells, we disrupted the activity of the androgen receptor with an antibody and an AR mRNA hammerhead ribozyme in the following cell lines: LNCaP (androgen-sensitive), LNCaP-Rf and LNCaP-C4 (androgen-refractory), and DU-145 (androgen-insensitive). Microinjection of either antibody or ribozyme inhibited proliferation of androgen-refractory cells. These findings demonstrate that the AR is critical for proliferation of androgen-refractory cells, even in the absence of androgens.
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M. E. Wright, M.-J. Tsai, and R. Aebersold Androgen Receptor Represses the Neuroendocrine Transdifferentiation Process in Prostate Cancer Cells Mol. Endocrinol., September 1, 2003; 17(9): 1726 - 1737. [Abstract] [Full Text] [PDF] |
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L. L. Xu, Y. Shi, G. Petrovics, C. Sun, M. Makarem, W. Zhang, I. A. Sesterhenn, D. G. McLeod, L. Sun, J. W. Moul, et al. PMEPA1, an Androgen-regulated NEDD4-binding Protein, Exhibits Cell Growth Inhibitory Function and Decreased Expression during Prostate Cancer Progression Cancer Res., August 1, 2003; 63(15): 4299 - 4304. [Abstract] [Full Text] [PDF] |
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L. Zhang, M. Johnson, K. H. Le, M. Sato, R. Ilagan, M. Iyer, S. S. Gambhir, L. Wu, and M. Carey Interrogating Androgen Receptor Function in Recurrent Prostate Cancer Cancer Res., August 1, 2003; 63(15): 4552 - 4560. [Abstract] [Full Text] [PDF] |
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W. G. Nelson, A. M. De Marzo, and W. B. Isaacs Prostate Cancer N. Engl. J. Med., July 24, 2003; 349(4): 366 - 381. [Full Text] [PDF] |
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I. V. Litvinov, A. M. De Marzo, and J. T. Isaacs Is the Achilles' Heel for Prostate Cancer Therapy a Gain of Function in Androgen Receptor Signaling? J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 2972 - 2982. [Full Text] [PDF] |
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R. E. Bakin, D. Gioeli, E. A. Bissonette, and M. J. Weber Attenuation of Ras Signaling Restores Androgen Sensitivity to Hormone-refractory C4-2 Prostate Cancer Cells Cancer Res., April 15, 2003; 63(8): 1975 - 1980. [Abstract] [Full Text] [PDF] |
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R. E. Bakin, D. Gioeli, R. A. Sikes, E. A. Bissonette, and M. J. Weber Constitutive Activation of the Ras/Mitogen-activated Protein Kinase Signaling Pathway Promotes Androgen Hypersensitivity in LNCaP Prostate Cancer Cells Cancer Res., April 15, 2003; 63(8): 1981 - 1989. [Abstract] [Full Text] [PDF] |
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L. Neckers Heat Shock Protein 90 Inhibition by 17-Allylamino-17- demethoxygeldanamycin: A Novel Therapeutic Approach for Treating Hormone-refractory Prostate Cancer : Commentary re: D. B. Solit et al., 17-Allylamino-17-demethoxygeldanamycin Induces the Degradation of Androgen Receptor and Her-2/neu and Inhibits the Growth of Prostate Cancer Xenografts. Clin. Cancer Res., 8: 986-993, 2002. Clin. Cancer Res., May 1, 2002; 8(5): 962 - 966. [Full Text] [PDF] |
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Y. B. Wetherill, C. E. Petre, K. R. Monk, A. Puga, and K. E. Knudsen The Xenoestrogen Bisphenol A Induces Inappropriate Androgen Receptor Activation and Mitogenesis in Prostatic Adenocarcinoma Cells Mol. Cancer Ther., May 1, 2002; 1(7): 515 - 524. [Abstract] [Full Text] [PDF] |
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