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Suppression of the androgen receptor function by quercetin through protein–protein interactions of Sp1, c-Jun, and the androgen receptor in human prostate cancer cells

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Abstract

We have previously reported that the increase in c-Jun expression induced by quercetin inhibited androgen receptor (AR) transactivation, and Sp1 was involved in quercetin-mediated downregulation of AR activity. Transient transfection assays in this work revealed that co-expression of c-Jun quenched Sp1-induced production of luciferase activity driven by AR promoter or three copies of Sp1 binding elements in the AR promoter. Moreover, c-Jun repressed AR-mediated luciferase activity via androgen-response elements (AREs) of the hK2 gene, while this suppression could be restored partially by cotransfection of Sp1 expression plasmid. The physical associations of c-Jun, Sp1, and AR induced by quercetin were further demonstrated by co-immunoprecipitation experiments. In addition, quercetin-mediated repression of AR expression and activity was partially reversed by blocking of JNK signaling pathway. These results suggested that c-Jun might play an important role in the suppression of AR expression and activity in the presence of quercetin, and association of a c-Jun/Sp1/AR protein complex induced by quercetin represented a novel mechanism that was involved in down-regulation of the AR function in prostate cancer cells.

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Abbreviations

AR:

Androgen receptor

ARE:

Androgen-response element

AP-1:

Activator protein-1

hK2:

Human glandular kallikrein

Mib:

Mibolerone

PSA:

Prostate-specific antigen

Sp1:

Promoter specificity protein 1

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Acknowledgments

This work was supported in part by NIH grant R01 88900, the National Natural Science Foundation of China (30772594), and Shandong Scientific Technology Program (2008GG10002042).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, 44 Wenhua westroad, 250012, Jinan, China

    Huiqing Yuan, Yuanyuan Tian, Zhifang Liu & Mengye Zhang

  2. Department of Urology, Mayo Clinic College of Medicine, Mayo Clinic/Foundation, Rochester, MN, 55905, USA

    Huiqing Yuan & Charles Y. F. Young

  3. Department of Natural Product of Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 Wenhua westroad, 250012, Jinan, China

    Hongxiang Lou

Authors
  1. Huiqing Yuan
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  2. Charles Y. F. Young
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  3. Yuanyuan Tian
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  4. Zhifang Liu
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Correspondence to Huiqing Yuan or Hongxiang Lou.

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Yuan, H., Young, C.Y.F., Tian, Y. et al. Suppression of the androgen receptor function by quercetin through protein–protein interactions of Sp1, c-Jun, and the androgen receptor in human prostate cancer cells. Mol Cell Biochem 339, 253–262 (2010). https://doi.org/10.1007/s11010-010-0388-7

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