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Tea polyphenols down-regulate the expression of the androgen receptor in LNCaP prostate cancer cells

Oncogene volume 19, pages 1924–1932 (2000)Cite this article

Abstract

Androgens via their cognate receptor may be involved in the development and progression of prostate cancer. The aim of this study was to determine whether tea polyphenols have inhibitory effects on androgen action in an androgen-responsive, prostate cancer cell line, LNCaP. The tea polyphenol, EGCG, inhibited LNCaP cell growth and the expression of androgen regulated PSA and hK2 genes. Moreover, EGCG had a significant inhibitory effect on the androgenic inducibility of the PSA promoter. Immunoblotting detected a decrease in androgen receptor protein with treatments of the tea polyphenols EGCG, GCG and theaflavins. Northern blot analysis showed decreased levels of androgen receptor mRNA by EGCG. Transient transfections demonstrated that EGCG and theaflavins could repress the transcriptional activities of the androgen receptor promoter region. An Sp1 binding site in the androgen receptor gene promoter is an important regulatory component for its expression. This study suggests Sp1 is the target for the tea polyphenols because treatments of EGCG decreased the expression, DNA binding activity and transactivation activity of Sp1 protein. In conclusion, we have described a new property of tea polyphenols that inhibits androgen action by repressing the transcription of the androgen receptor gene.

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Acknowledgements

This work is partly supported by the NIH grants DK 41995 and CA 70982.

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Authors and Affiliations

  1. Department of Urology, Mayo Graduate School, Mayo Foundation, Rochester, 55905, Minnesota, MN, USA

    Fengge Ren, Shaobo Zhang, Susan H Mitchell, Rachel Butler & Charles YF Young

  2. Department of Biochemistry and Molecular Biology, Mayo Graduate School, Mayo Foundation, Rochester, 55905, Minnesota, MN, USA

    Fengge Ren, Shaobo Zhang, Susan H Mitchell, Rachel Butler & Charles YF Young

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  1. Fengge Ren
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Ren, F., Zhang, S., Mitchell, S. et al. Tea polyphenols down-regulate the expression of the androgen receptor in LNCaP prostate cancer cells. Oncogene 19, 1924–1932 (2000). https://doi.org/10.1038/sj.onc.1203511

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