ART-27, An Androgen Receptor Coactivator Regulated in Prostate Development and Cancer

Samir S. Taneja, Susan Ha, Nicole K. Swenson, Inés Pineda Torra, Serge Rome, Paul D. Walden, Hong Ying Huang, Ellen Shapiro, Michael J. Garabedian, Susan K. Logan

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Androgen receptor trapped clone-27 (ART-27) is a newly described transcriptional coactivator that binds to the N terminus of the androgen receptor (AR). Given the vital importance of AR signaling in prostate growth and differentiation, we investigated the role of ART-27 in these processes. Immunohistochemical studies indicate that ART-27 protein is expressed in differentiated epithelial cells of adult human prostate and breast tissue. In prostate, ART-27 is abundant in AR-positive prostate luminal epithelial cells, in contrast to the stroma, where cells express AR but not ART-27. The use of a rat model of androgen depletion/reconstitution indicates that ART-27 expression is associated with the elaboration of differentiated prostate epithelial cells. Interestingly, regulated expression of ART-27 in the androgen. sensitive LNCaP prostate cancer cell line inhibits androgen-mediated cellular proliferation and enhances androgen-mediated transcription of the prostate-specific antigen (PSA) gene. Consistent with a growth suppressive function, we show that ART-27 expression levels are negligible in human prostate cancer. Importantly, examination of ART-27 protein expression in early fetal prostate development demonstrates that ART-27 is detected only when the developing prostate gland has proceeded from a solid mass of undifferentiated cells to a stage in which differentiated luminal epithelial cells are evident. Thus, ART-27 is an AR cofactor shown to be subject to both cell type and developmental regulation in humans. Overall, the results suggest that decreased levels of ART-27 protein in prostate cancer tissue may occur as a result of de-differentiation, and indicate that ART-27 is likely to regulate a subset of AR-responsive genes important to prostate growth suppression and differentiation.

    Original languageEnglish (US)
    Pages (from-to)13944-13952
    Number of pages9
    JournalJournal of Biological Chemistry
    Volume279
    Issue number14
    DOIs
    StatePublished - Apr 2 2004

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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