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Negative Androgen-Response Elements in Androgen Target Genes

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Androgen-Responsive Genes in Prostate Cancer

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Abstract

Genes that are positively regulated by androgen receptor (AR) contain the positive androgen-response element (pARE) in their proximal or/and distal promoter regions. Similarly, genes that are negatively regulated by AR contain the negative androgen-response element (nARE). In this chapter, we review our work on identification and characterization of nARE. We identified seven nAREs in the negative androgen-response region in the TGF-β1 promoter. Each nARE is composed of 15 nucleotides and mediates androgen-dependent inhibition of transcription. The 5′ portions of nAREs are highly conserved and resemble core half-sites in pAREs. The nAREs interacted weakly with AR DNA-binding domain (AR DBD) in gel shift assays. Mutations on the conserved nucleotides in the nARE abolished its interaction with the AR DBD and abolished its inhibition of androgen-driven transcription, suggesting that nARE/AR interaction is essential for nARE-mediated inhibition of transcription. Taken together, these findings indicate that the AR negatively regulates the expression of its target genes via a negative androgen-response region composed of multiple nAREs.

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Authors and Affiliations

  1. Departments of Urology, The University of Texas M.D. Anderson Cancer Center Houston, Houston, TX, 77030, USA

    Wei Qi

  2. Departments of Cancer Biology, Unit 173, The University of Texas M.D. Anderson Cancer Center Houston, Houston, TX, 77030, USA

    Zhengxin Wang

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  1. Wei Qi
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  2. Zhengxin Wang
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Correspondence to Zhengxin Wang .

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Editors and Affiliations

  1. , Shadyside Medical Center, University of Pittsburgh, Centre Ave 5200, Pittsburgh, 15232, Pennsylvania, USA

    Zhou Wang

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Qi, W., Wang, Z. (2013). Negative Androgen-Response Elements in Androgen Target Genes. In: Wang, Z. (eds) Androgen-Responsive Genes in Prostate Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6182-1_3

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