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.
Heitzer
Marjet D
MD
Department of Cell Biology and Physiology and Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
DeFranco
Donald B
DB
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D051523:Fibroblast Growth Factor 7 / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D015533:Transcriptional Activation
D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D011944:Receptors, Androgen; C490351:TGFB1I1 protein, human; D051523:Fibroblast Growth Factor 7