The androgen receptor (AR) is a ligand-controlled transcription factor that is required for normal development ofthe prostate. It is expressed in both A-dependent and -independent prostate cancer (PCA) cells. Emerging data suggest AR regulates growth of PCA cells even in the absence ofAs, implying it is activated by factors other than As. Herein, we show that stimulation of A-dependent PCA LNCaP cells with reagents that promote accumulation of cyclic adenosine monophosphate (cAMP) leads to protein kinase A (PKA)-dependent activation of AR. Importantly, dihydrotestosterone (DHT)-regulated activation of AR also required PKA. Stimulation with epidermal growth factor, that robustly activates extracellular signal-regulated kinase pathway, did not promote activation of AR. These data establish a critical role for PKA in AR activation and suggest it may contribute to the growth of A-independent prostate tumors.

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