The androgen receptor co-activator CBP is up-regulated following androgen withdrawal and is highly expressed in advanced prostate cancer
The androgen receptor co-activator CBP is up-regulated following androgen withdrawal and is highly expressed in advanced prostate cancer
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DOI：
10.1002/path.1609
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发表时间：
2004-10-01
影响因子：
7.3
通讯作者：
Hobisch, A
中科院分区：
文献类型：
--
作者：
Comuzzi, B;Nemes, C;Hobisch, A
雄激素受体共激活剂CREB（cAMP-反应元件结合蛋白）结合蛋白（CBP）在雄激素和雄激素受体拮抗剂刺激后增强雄激素受体活性。本研究的目的是研究类固醇和肽类激素对前列腺癌CBP表达的调节。为此，LNCaP细胞用合成雄激素甲基三烯醇酮（R1881）、表皮生长因子、胰岛素样生长因子-I或白细胞介素-6（IL-6）处理。Western blotting和real-time PCR检测CBP蛋白和mRNA的表达。CBP的表达也进行了研究，从26例患者的前列腺癌的治疗耐药的组织标本。在LNCaP细胞中，CBP蛋白被R1881或IL-6下调。非甾体类抗雄激素比卡鲁胺拮抗R1881的作用，Janus激酶抑制剂AG 490逆转IL-6的作用。相反，R1881和IL-6均未对PC-3细胞系中CBP的表达产生任何影响。在LNCaP细胞中，R1881或IL-6也在mRNA水平上观察到CBP表达的抑制。免疫组化法检测26例标本CBP蛋白表达。结果表明，雄激素消融过程中CBP的上调可能与前列腺癌患者内分泌治疗的失败有关。版权所有（C）2004大不列颠和爱尔兰病理学会。出版社：John Wiley Sons，Ltd
The androgen receptor co-activator CREB (cAMP-response element binding protein)binding protein (CBP) enhances androgen receptor activity after stimulation by androgenic hormones and androgen receptor antagonists. The aim of the present study was to investigate the regulation of CBP expression by steroid and peptide hormones in prostate cancer. For this purpose, LNCaP cells were treated with the synthetic androgen methyltrienolone (R1881), epidermal growth factor, insulin-like growth factor-I or interleukin-6 (IL-6). CBP protein and mRNA expression were studied by western blotting and real-time PCR, respectively. CBP expression was also investigated in tissue specimens obtained from 26 patients with therapy-resistant carcinoma of the prostate. In LNCaP cells, CBP protein was down-regulated by R1881 or IL-6. The non-steroidal anti-androgen bicalutamide antagonized the effects of R1881 and the Janus kinase inhibitor AG 490 reversed the effects of IL-6. In contrast, neither R1881 nor IL-6 caused any effect on CBP expression in the PC-3 cell line. In LNCaP cells, the inhibition of CBP expression by R1881 or IL-6 was also observed at the mRNA level. CBP protein was detected in all 26 specimens by immunohistochemistry. The results suggest that up-regulation of CBP during androgen ablation may be relevant to the failure of endocrine therapy in patients with prostate carcinoma. Copyright (C) 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley Sons, Ltd.