Expression of androgen receptor coregulatory proteins in prostate cancer and stromal-cell culture models

BACKGROUND. Androgen receptor (AR) transcriptional activity is modulated by cofactor proteins. They act as costimulators, corepressors, or bridging pr oteins, 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, includ ing several LNCaP sublines, and in prostate stromal cells. METHODS. Expression of cofactors was analyzed by means of RT-PCR in PC-3, D u-145, LNCaP, three sublines of LNCaP established after long-term androgen deprivation, and two strains of primary prostate stroma cells. Expression i n 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 analyze d (AIB1, ARA54, ARA70, CBP, cyclin D1, Her2/neu/erbB2, BAG-1/M/L, SRC-1, SM RT, and TIF2). Only ARA55 and FHL2 mRNAs were not detected in all cells. AR A55 mRNA was absent in LNCaP cells, LNCaP sublines, and DU-145 cells; FHL2 was not expressed in LNCaP cells and its derivatives. The expression patter n was identical in LNCaP cells, and the long-term androgen ablated LNCaP su blines. Moreover, comparison of expression levels in LNCaP and LNCaP-abl ce lls revealed a slight reduction in LNCaP-abl cells but no gross differences . CONCLUSIONS. Prostatic cells express a great number of steroid receptor cof actors. AR activity thus seems to be modulated in a very complex way in pro state cells. Prostate 45:124-131, 2000. (C) 2000 Wiley-Liss, Inc.