Genome-wide impact of androgen receptor trapped clone-27 loss on androgen-regulated transcription in prostate cancer cells

Jerome C. Nwachukwu, Paolo Mita, Rachel Ruoff, Susan Ha, Qianben Wang, S. Joseph Huang, Samir S. Taneja, Myles Brown, William L. Gerald, Michael J. Garabedian, Susan K. Logan

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    Abstract

    The androgen receptor (AR) directs diverse biological pro-cesses through interaction with coregulators such as AR trapped clone-27 (ART-27). Our results show that ART-27 is recruited to AR-binding sites by chromatin immunoprecipi-tation analysis. In addition1 the effect of ART-27 on genome-wide transcription was examined. The studies indicate that loss of ART-27 enhances expression of many androgen-regulated genes, suggesting that ART-27 inhibits gene expression. Surprisingly, classes of genes that are up-regulated upon ART-27 depletion include regulators of DNA damage check-point and cell cycle progression1 suggesting that ART-27 functions to keep expression levels of these genes low. Consistent with this idea, stable reduction of ART-27 by short-hairpin RNA enhances LNCaP cell proliferation com-pared with control cells. The effect of ART-27 loss was also examined in response to the antiandrogen bicalutamide.Unexpectedly, cells treated with ART-27 siRNA no longer exhibited gene repression in response to bicalutamide. To examine ART-27 loss in prostate cancer progression1 immu-nohistochemistry was conducted on a tissue array containing samples from primary tumors of individuals who were clinically followed and later shown to have either recurrent or nonrecurrent disease. Comparison of ART-27 and AR staining indicated that nuclear ART-27 expression was lost in the majority of AR-positive recurrent prostate cancers. Our studies show that reduction of ART-27 protein levels in prostate cancer may facilitate antiandrogen-resistant disease.

    Original languageEnglish (US)
    Pages (from-to)3140-3147
    Number of pages8
    JournalCancer Research
    Volume69
    Issue number7
    DOIs
    StatePublished - Apr 1 2009

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    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

    Cite this

    Nwachukwu, J. C., Mita, P., Ruoff, R., Ha, S., Wang, Q., Huang, S. J., Taneja, S. S., Brown, M., Gerald, W. L., Garabedian, M. J., & Logan, S. K. (2009). Genome-wide impact of androgen receptor trapped clone-27 loss on androgen-regulated transcription in prostate cancer cells. Cancer Research, 69(7), 3140-3147. https://doi.org/10.1158/0008-5472.CAN-08-3738