雄激素受体相关蛋白55（ARA55）与雄激素受体在前列腺癌中的表达

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

作者信息

Miyoshi Yasuhide, Ishiguro Hitoshi, Uemura Hiroji, Fujinami Kiyoshi, Miyamoto Hiroshi, Miyoshi Yoshiko, Kitamura Hitoshi, Kubota Yoshinobu

机构信息

Department of Urology, Yokohama City University School of Medicine, Kanazawa-ku, Yokohama, Japan.

出版信息

Prostate. 2003 Sep 1;56(4):280-6. doi: 10.1002/pros.10262.

DOI:10.1002/pros.10262

PMID:12858356

Abstract

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.

摘要

背景

雄激素受体（AR）转录受多种辅因子调控，如AR相关蛋白（ARA），包括ARA70、ARA54和ARA55。ARA55可增加AR转录并改变配体特异性。我们推测ARA55可能在前列腺癌的发生或发展中起重要作用。我们评估了ARA55在前列腺癌组织中的信使核糖核酸（mRNA）表达，并分析了ARA55表达与临床特征之间的关系。

方法

共检测了30份前列腺癌标本（20份未经治疗的前列腺癌和10份复发性激素难治性前列腺癌（HRPC））以及5份良性前列腺增生（BPH）组织样本。使用实时定量逆转录聚合酶链反应（RT-PCR）分析ARA55和AR的mRNA表达。

结果

在所有未经治疗的前列腺癌、HRPC和BPH组织样本中均检测到ARA55表达。使用定量PCR检测发现，HRPC标本中ARA55表达水平显著低于未经治疗的前列腺癌（P = 0.02）或BPH（P = 0.005）样本。另一方面，在HRPC患者中，较高的ARA55表达与较短的无复发生存期（P = 0.02）和总生存期（P = 0.01）相关。在前列腺癌和BPH的所有标本中也均检测到AR表达。HRPC样本中的AR表达水平显著高于未经治疗的前列腺癌（P = 0.001）和BPH（P = 0.01）样本。

结论

ARA55可能与前列腺癌的发生和发展有关。HRPC标本中ARA55表达水平显著低于未经治疗的前列腺癌或BPH标本。相反，我们的结果表明，较高的ARA55表达水平可能导致HRPC患者无复发生存期和总生存期不佳。ARA55在前列腺癌发生和进展至激素难治状态过程中的作用可能不同。这些数据不仅有助于理解前列腺癌发生或复发的分子机制，还可能为激素难治性复发性前列腺癌带来治疗策略。