Suppression of Androgen Receptor Transactivation and Prostate Cancer Cell Growth by Heterogeneous Nuclear Ribonucleoprotein A1 via Interaction with Androgen

The androgen receptor (AR) requires coregulators for its optimal transactivation. Whether AR coregulators also need interacting proteins to modulate their function remains un-clear. Here we describe heterogeneous nuclear ribonucleo-protein (hnRNP) A1 as an associated negative modulator for the AR coregulator ARA54. hnRNP A1 selectively suppressed ARA54-enhanced wild-type and mutant AR transactivation via interruption of AR-ARA54 interaction and ARA54 homodimerization. Stable transfection of hnRNP A1 in the LNCaP cells suppressed AR-mediated cell growth and the ex-pression of prostate-specific antigen, and this suppressive ef-fect was abolished by the addition of ARA54-small interfering RNA. Small interfering RNA knockdown of endogenous hnRNPA1enhancedcell growthandprostate-specific antigen expression in LNCaP cells. These results not only suggest tha