Differential induction of androgen receptor transactivation by different androgen receptor coactivators in human prostate cancer DU145 cells

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

Research output: Contribution to journalArticle

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 ARA70 is the best coactivator to confer the androgenic activity on 17β- estradiol. Only ARA70 and ARA55 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 ARA54, but not steroid receptor coactivator-1 (SRC-1) and Rb, could significantly enhance the Δ 5-androstenediol-mediated AR transactivation. Furthermore, in comparing the relative specificity of these coactivators to AR in DU145 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.

Original languageEnglish (US)
Pages (from-to)195-202
Number of pages8
JournalEndocrine
Volume11
Issue number2
StatePublished - 1999
Externally publishedYes

Fingerprint

Androgen Receptors
Transcriptional Activation
Androgen Antagonists
Prostatic Neoplasms
Gonadal Steroid Hormones
Nuclear Receptor Coactivator 1
Androstenediol
Chromatin Assembly and Disassembly
Steroid Receptors
Transferases
Histones
Glucocorticoids
Androgens
Progesterone
Estradiol

Keywords

  • Δ -androstenediol
  • 17β- estradiol
  • Androgen receptor
  • Antiandrogen
  • Coactivator
  • p300/CBP-associated factor
  • Steroid specificity

ASJC Scopus subject areas

  • Endocrinology

Cite this

Yeh, S., Kang, H. Y., Miyamoto, H., Nishimura, K., Chang, H. C., Ting, H. J., ... Chang, C. (1999). Differential induction of androgen receptor transactivation by different androgen receptor coactivators in human prostate cancer DU145 cells. Endocrine, 11(2), 195-202.

Differential induction of androgen receptor transactivation by different androgen receptor coactivators in human prostate cancer DU145 cells. / Yeh, Shuyuan; Kang, Hong Yo; Miyamoto, Hiroshi; Nishimura, Kazuo; Chang, Hong Chiang; Ting, Huei Ju; Rahman, Mujib; Lin, Hui Kuan; Fujimoto, Naohiro; Hu, Yueh Chiang; Mizokami, Atsushi; Huang, Ko En; Chang, Chawnshang.

In: Endocrine, Vol. 11, No. 2, 1999, p. 195-202.

Research output: Contribution to journalArticle

Yeh, S, Kang, HY, Miyamoto, H, Nishimura, K, Chang, HC, Ting, HJ, Rahman, M, Lin, HK, Fujimoto, N, Hu, YC, Mizokami, A, Huang, KE & Chang, C 1999, 'Differential induction of androgen receptor transactivation by different androgen receptor coactivators in human prostate cancer DU145 cells', Endocrine, vol. 11, no. 2, pp. 195-202.
Yeh, Shuyuan ; Kang, Hong Yo ; Miyamoto, Hiroshi ; Nishimura, Kazuo ; Chang, Hong Chiang ; Ting, Huei Ju ; Rahman, Mujib ; Lin, Hui Kuan ; Fujimoto, Naohiro ; Hu, Yueh Chiang ; Mizokami, Atsushi ; Huang, Ko En ; Chang, Chawnshang. / Differential induction of androgen receptor transactivation by different androgen receptor coactivators in human prostate cancer DU145 cells. In: Endocrine. 1999 ; Vol. 11, No. 2. pp. 195-202.
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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 ARA70 is the best coactivator to confer the androgenic activity on 17β- estradiol. Only ARA70 and ARA55 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 ARA54, but not steroid receptor coactivator-1 (SRC-1) and Rb, could significantly enhance the Δ 5-androstenediol-mediated AR transactivation. Furthermore, in comparing the relative specificity of these coactivators to AR in DU145 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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AU - Yeh, Shuyuan

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AU - Miyamoto, Hiroshi

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AU - Chang, Hong Chiang

AU - Ting, Huei Ju

AU - Rahman, Mujib

AU - Lin, Hui Kuan

AU - Fujimoto, Naohiro

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AU - Mizokami, Atsushi

AU - Huang, Ko En

AU - Chang, Chawnshang

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AB - 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 ARA70 is the best coactivator to confer the androgenic activity on 17β- estradiol. Only ARA70 and ARA55 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 ARA54, but not steroid receptor coactivator-1 (SRC-1) and Rb, could significantly enhance the Δ 5-androstenediol-mediated AR transactivation. Furthermore, in comparing the relative specificity of these coactivators to AR in DU145 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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