Expression of AR associated protein 55 (ARA55) and androgen receptor in prostate cancer

Background: Androgen receptor (AR) transcription is modulated by several cofactors such as AR associated proteins (ARA) including ARA70, ARA54, and ARA55. ARA55 increases AR transcription and alters ligand specificity. We hypothesized that ARA55 might play an important role in prostate cancer development or progression. We evaluated the messenger RNA (mRNA) expression of ARA55 in prostate cancer tissues, and analyzed the relation between ARA55 expression and clinical characteristics.

Methods: A total of 30 prostate cancer specimens (20 previously untreated prostate cancers and 10 recurrent, hormone-refractory prostate cancers (HRPC)) and 5 benign prostatic hypertrophy (BPH) tissue samples were examined. mRNA expression of ARA55 and AR were analyzed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) using real time PCR.

Results: ARA55 expression was identified in all tissue samples of previously untreated prostate cancer, HRPC and BPH. ARA55 expression level in HRPC specimens was significantly lower than that in previously untreated prostate cancer (P = 0.02) or BPH (P = 0.005) samples using quantitative PCR. On the other hand, higher ARA55 expression was associated with shorter recurrence-free survival (P = 0.02) and overall survival (P = 0.01) in HRPC patients. AR expression was also revealed in all specimens of both prostate cancer and BPH. AR expression level in HRPC samples was significantly higher than that in previously untreated prostate cancer (P = 0.001) and BPH (P = 0.01) samples.

Conclusions: ARA55 may be associated with prostate cancer development and progression. ARA55 expression level in HRPC specimens was significantly lower than that in previously untreated prostate cancer or BPH specimens. On the contrary, our results suggested that a higher ARA55 expression level may result in unfavorable recurrence-free survival and overall survival in HRPC patients. The role of ARA55 may differ between prostate cancer development and the process of progression to a hormone-refractory state. These data not only help to understand the molecular mechanism of prostate cancer development or recurrence, but may also lead to a therapeutic strategy for recurrent prostate cancer that is refractory to hormonal treatment.