Background: Androgen receptor (AR) transcriptional activity is modulated by cofactor proteins. They act as costimulators, corepressors, or bridging proteins, and a disbalanced expression may contribute to the altered activity of the AR in advanced prostate cancer. We investigated the expression of a series of steroid receptor cofactors in prostate cancer cell lines, including several LNCaP sublines, and in prostate stromal cells.
Methods: Expression of cofactors was analyzed by means of RT-PCR in PC-3, Du-145, LNCaP, three sublines of LNCaP established after long-term androgen deprivation, and two strains of primary prostate stroma cells. Expression in LNCaP and LNCaP-abl cells (which represented an advanced tumor cell) was analyzed employing semiquantitative RT-PCR.
Results: Ten of the 12 cofactors tested were expressed in all cells analyzed (AIB1, ARA54, ARA70, CBP, cyclin D1, Her2/neu/erbB2, BAG-1/M/L, SRC-1, SMRT, and TIF2). Only ARA55 and FHL2 mRNAs were not detected in all cells. ARA55 mRNA was absent in LNCaP cells, LNCaP sublines, and DU-145 cells; FHL2 was not expressed in LNCaP cells and its derivatives. The expression pattern was identical in LNCaP cells, and the long-term androgen ablated LNCaP sublines. Moreover, comparison of expression levels in LNCaP and LNCaP-abl cells revealed a slight reduction in LNCaP-abl cells but no gross differences.
Conclusions: Prostatic cells express a great number of steroid receptor cofactors. AR activity thus seems to be modulated in a very complex way in prostate cells.
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