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Keywords:

  • androgen receptor;
  • coactivator;
  • prostate cancer;
  • prostate cells culture;
  • hormonal regulation

Abstract

BACKGROUND

In prostate cancer cell lines, androgen receptor (AR) coactivators modulate the transcriptional activity of AR. However, very little is known about their expression in normal prostate tissue and during progression to cancer.

METHODS

AR and coactivators ARA54, ARA55, ARA70, and SRC1 RNA were analyzed by RT-PCR in normal and tumoral tissues of the same prostate, in prostate cell lines, and after hormonal treatments of prostate epithelial cells.

RESULTS

AR-coactivators were expressed in normal and tumoral tissues and in cultured prostate cells; only ARA55 expression was decreased in tumoral relative to normal tissue of all seven prostates analyzed. It was not expressed in LNCaP and DU145 cancer cells and low in PNT2 immortalized cells in which all coactivator's expression were down regulated by DHT and up regulated by E2. In addition, coactivator's expression was increased in hyperplastic relative to normal prostate fibroblasts.

CONCLUSIONS

ARA55 is both an AR coactivator and a focal adhesion protein (Hic-5). Its role in the progression of prostate carcinoma may therefore involve these two different functions. Its decrease in cancer tissue suggests that it plays a different role than that expected, namely, facilitate cell proliferation and therefore mobility and metastasis. Prostate 56: 192–200, 2003. © 2003 Wiley-Liss, Inc.