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Differential induction of androgen receptor transactivation by different androgen receptor coativators in human prostate cancer DU 145 cells

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Abstract

Recently identified androgen receptor (AR) coactivators were used in this study to determine whether the specificity of sex hormones and antiandrogens could be modulated at the coactivator level. We found that ARA 70 is the best coactivator to confer the androgenic activity on 17β-estradiol. Only ARA 70 and ARA 55 could increase significantly the androgenic activity of hydroxyflutamide, a widely used antiandrogen for the treatment of prostate cancer. None of the AR coactivators we tested could significantly confer androgenic activity on progesterone and glucocorticoid at their physiological concentrations (1–10 nM). We also found that ARA70, ARA55, and ARA 54, but not steroid receptor coactivator-1 (SRC-1) and Rb, could significantly enhance the Δ5-androstenediol-mediated AR transactivation. Furthermore, in comparing the relative specificity of these coactivators to AR in DU 145 cells, our results suggested that ARA70 has a relatively higher specificity and that SRC-1 can enhance almost equally well many other steroid receptors. Finally, our data demonstrated that AR itself and some select AR coactivators such as ARA70 or ARA54 could, respectively, interact with CBP and p300/CBP-associated factors that have histone acetyl-transferase activity for assisting chromatin remodeling. Together, our data suggest that the specificity of sex hormones and antiandrogens can be modulated by some selective AR coactivators. These findings may not only help us to better understand the specificity of the sex hormones and antiandrogens, but also facilitate the development of better antiandrogens to fight the androgen-related diseases, such as prostate cancer.

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Authors and Affiliations

  1. George Whipple Laboratory for Cancer Research, Department of Pathology, University of Rochester, 14642, Roschester, NY

    Shuyuan Yeh, Hong-Yo Kang, Hiroshi Miyamoto, Kazuo Nishimura, Hong-Chiang Chang, Huei-Ju Ting, Mujib Rahman, Hui-Kuan Lin, Naohiro Fujimoto, Yueh-Chiang Hu, Atsushi Mizokami, Ko-En Huang & Chawnshang Chang

  2. Department of Urology, University of Rochester, 14642, Roschester, NY

    Shuyuan Yeh, Hong-Yo Kang, Hiroshi Miyamoto, Kazuo Nishimura, Hong-Chiang Chang, Huei-Ju Ting, Mujib Rahman, Hui-Kuan Lin, Naohiro Fujimoto, Yueh-Chiang Hu, Atsushi Mizokami, Ko-En Huang & Chawnshang Chang

  3. Department of Radiation Oncology, University of Rochester, 14642, Rochester, NY

    Shuyuan Yeh, Hong-Yo Kang, Hiroshi Miyamoto, Kazuo Nishimura, Hong-Chiang Chang, Huei-Ju Ting, Mujib Rahman, Hui-Kuan Lin, Naohiro Fujimoto, Yueh-Chiang Hu, Atsushi Mizokami, Ko-En Huang & Chawnshang Chang

  4. Department of the Cancer Center, University of Rochester, 14642, Rochester, NY

    Shuyuan Yeh, Hong-Yo Kang, Hiroshi Miyamoto, Kazuo Nishimura, Hong-Chiang Chang, Huei-Ju Ting, Mujib Rahman, Hui-Kuan Lin, Naohiro Fujimoto, Yueh-Chiang Hu, Atsushi Mizokami, Ko-En Huang & Chawnshang Chang

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  1. Shuyuan Yeh
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Correspondence to Chawnshang Chang.

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Yeh, S., Kang, HY., Miyamoto, H. et al. Differential induction of androgen receptor transactivation by different androgen receptor coativators in human prostate cancer DU 145 cells. Endocr 11, 195–202 (1999). https://doi.org/10.1385/ENDO:11:2:195

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  • DOI: https://doi.org/10.1385/ENDO:11:2:195

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