Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Heitzer, M.D. et al.

Hic-5/ ARA55, a LIM domain-containing nuclear receptor coactivator expressed in prostate stromal cells.

Prostate gland development and growth requires both androgen action and epithelial-stromal communications. In fact, androgen signaling through the androgen receptor ( AR) may be important in both stromal and epithelial cells of the prostate. Because interaction of AR with the coactivator, Hic-5/ ARA55, results in enhanced androgen-induced transcription, we analyzed Hic-5/ ARA55 expression in prostate tissue sections from normal human donors and prostate cancer patients. In each sample, Hic-5/ ARA55 expression was confined to the stromal compartment of the prostate. Furthermore, a prostate stromal cell line, WPMY-1 cells, expresses Hic-5/ ARA55, which is localized both at focal adhesion complexes and within the soluble cytoplasmic compartment. The ability of Hic-5/ ARA55 to shuttle between the nuclear and cytoplasmic compartments was revealed on inhibition of nuclear export with leptomycin B. Small interfering RNA ablation experiments established endogenous Hic-5/ ARA55 as a coactivator for both viral and endogenous cellular AR-regulated genes. Finally, the mechanism of Hic-5/ ARA55 coactivator activity in WPMY-1 cells was revealed by chromatin immunoprecipitation analysis that showed its androgen-dependent recruitment to the promoter of the stromal androgen-responsive keratinocyte growth factor gene. These data provide the first demonstration of a stromal-specific AR coactivator that has an effect on an androgen-regulated growth factor that is essential for stromal/epithelial cell communication in the prostate.[1]

References

Hic-5/ARA55, a LIM domain-containing nuclear receptor coactivator expressed in prostate stromal cells. Heitzer, M.D., DeFranco, D.B. Cancer Res. (2006) [Pubmed]

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