Androgen receptor (AR) NH2- and COOH-terminal interactions result in the differential influences on the AR-mediated transactivation and cell growth

Cheng Lung Hsu, Yuh-Ling Chen, Huei Ju Ting, Wen Jye Lin, Zhiming Yang, Yanqing Zhang, Liang Wang, Chun Te Wu, Hong Chiang Chang, Shuyuan Yeh, Sanjay W. Pimplikar, Chawnshang Chang

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Abstract

Early reports showed that androgen receptor (AR) NH2- and COOH-terminal (N-C) interaction was important for full AR function. However, the influence of these interactions on the AR in vivo effects remains unclear. Here we tested some AR-associated peptides and coregulators to determine their influences on AR N-C interaction, AR transactivation, and AR coregulator function. The results showed that AR coactivators such as ARA70N, gelsolin, ARA54, and SRC-1 can enhance AR transactivation but showed differential influences on the N-C interaction. In contrast, AR corepressors ARA67 and Rad9 can suppress AR transactivation, with ARA67 enhancing and Rad9 suppressing AR N-C interaction. Furthermore, liganded AR C terminus-associated peptides can block AR N-C interaction, but only selective peptides can block AR transactivation and coregulator function. We found all the tested peptides can suppress prostate cancer LNCaP cell growth at different levels in the presence of 5α-dihydrotestosterone, but only the tested FXXLF-containing peptides, not FXXMF-containing peptides, can suppress prostate cancer CWR22R cell growth. Together, these results suggest that the effects of AR N-C interactions may not always correlate with similar effects on AR-mediated transactivation and/or AR-mediated cell growth. Therefore, drugs designed by targeting AR N-C interaction as a therapeutic intervention for prostate cancer treatment may face unpredictable in vivo effects.

Original languageEnglish
Pages (from-to)350-361
Number of pages12
JournalMolecular Endocrinology
Volume19
Issue number2
DOIs
Publication statusPublished - 2005 Feb 1

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Androgen Receptors
Transcriptional Activation
Growth
Peptides
Prostatic Neoplasms
Gelsolin
Co-Repressor Proteins
Dihydrotestosterone
Drug Delivery Systems

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Endocrinology

Cite this

Hsu, Cheng Lung ; Chen, Yuh-Ling ; Ting, Huei Ju ; Lin, Wen Jye ; Yang, Zhiming ; Zhang, Yanqing ; Wang, Liang ; Wu, Chun Te ; Chang, Hong Chiang ; Yeh, Shuyuan ; Pimplikar, Sanjay W. ; Chang, Chawnshang. / Androgen receptor (AR) NH2- and COOH-terminal interactions result in the differential influences on the AR-mediated transactivation and cell growth. In: Molecular Endocrinology. 2005 ; Vol. 19, No. 2. pp. 350-361.
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abstract = "Early reports showed that androgen receptor (AR) NH2- and COOH-terminal (N-C) interaction was important for full AR function. However, the influence of these interactions on the AR in vivo effects remains unclear. Here we tested some AR-associated peptides and coregulators to determine their influences on AR N-C interaction, AR transactivation, and AR coregulator function. The results showed that AR coactivators such as ARA70N, gelsolin, ARA54, and SRC-1 can enhance AR transactivation but showed differential influences on the N-C interaction. In contrast, AR corepressors ARA67 and Rad9 can suppress AR transactivation, with ARA67 enhancing and Rad9 suppressing AR N-C interaction. Furthermore, liganded AR C terminus-associated peptides can block AR N-C interaction, but only selective peptides can block AR transactivation and coregulator function. We found all the tested peptides can suppress prostate cancer LNCaP cell growth at different levels in the presence of 5α-dihydrotestosterone, but only the tested FXXLF-containing peptides, not FXXMF-containing peptides, can suppress prostate cancer CWR22R cell growth. Together, these results suggest that the effects of AR N-C interactions may not always correlate with similar effects on AR-mediated transactivation and/or AR-mediated cell growth. Therefore, drugs designed by targeting AR N-C interaction as a therapeutic intervention for prostate cancer treatment may face unpredictable in vivo effects.",
author = "Hsu, {Cheng Lung} and Yuh-Ling Chen and Ting, {Huei Ju} and Lin, {Wen Jye} and Zhiming Yang and Yanqing Zhang and Liang Wang and Wu, {Chun Te} and Chang, {Hong Chiang} and Shuyuan Yeh and Pimplikar, {Sanjay W.} and Chawnshang Chang",
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Hsu, CL, Chen, Y-L, Ting, HJ, Lin, WJ, Yang, Z, Zhang, Y, Wang, L, Wu, CT, Chang, HC, Yeh, S, Pimplikar, SW & Chang, C 2005, 'Androgen receptor (AR) NH2- and COOH-terminal interactions result in the differential influences on the AR-mediated transactivation and cell growth', Molecular Endocrinology, vol. 19, no. 2, pp. 350-361. https://doi.org/10.1210/me.2004-0190

Androgen receptor (AR) NH2- and COOH-terminal interactions result in the differential influences on the AR-mediated transactivation and cell growth. / Hsu, Cheng Lung; Chen, Yuh-Ling; Ting, Huei Ju; Lin, Wen Jye; Yang, Zhiming; Zhang, Yanqing; Wang, Liang; Wu, Chun Te; Chang, Hong Chiang; Yeh, Shuyuan; Pimplikar, Sanjay W.; Chang, Chawnshang.

In: Molecular Endocrinology, Vol. 19, No. 2, 01.02.2005, p. 350-361.

Research output: Contribution to journalArticle

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AU - Hsu, Cheng Lung

AU - Chen, Yuh-Ling

AU - Ting, Huei Ju

AU - Lin, Wen Jye

AU - Yang, Zhiming

AU - Zhang, Yanqing

AU - Wang, Liang

AU - Wu, Chun Te

AU - Chang, Hong Chiang

AU - Yeh, Shuyuan

AU - Pimplikar, Sanjay W.

AU - Chang, Chawnshang

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