Expression of androgen receptor coregulators in prostate cancer
Expression of androgen receptor coregulators in prostate cancer
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DOI：
10.1158/1078-0432.ccr-0990-3
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发表时间：
2004-02-01
影响因子：
11.5
通讯作者：
Visakorpi, T
中科院分区：
文献类型：
--
作者：
Linja, MJ;Porkka, KP;Visakorpi, T
目的：雄激素受体（AR）介导的信号通路似乎在前列腺癌的发生和发展中起着至关重要的作用。体外研究表明，AR共调节因子表达的改变可能显著改变AR的转录活性，这提示这些共调节因子也可能促进前列腺癌的进展。在此，我们的目的是评估体内前列腺癌中AR共调节因子表达的变化。
实验设计：通过实时定量逆转录 - 聚合酶链反应（RT - qPCR）测量16种AR共激活因子和共抑制因子（SRC1、β - 连环蛋白、TIF2、PIAS1、PIASx、ARIP4、BRCA1、AIB1、AIB3、CBP、STAT1、NCoR1、AES、细胞周期蛋白D1、p300和ARA24）在前列腺癌细胞系、异种移植物以及临床前列腺肿瘤标本中的表达。此外，通过荧光原位杂交分析SRC1的基因拷贝数。
结果：AR阳性和AR阴性的细胞系及异种移植物均表达共调节因子。所研究的大多数共调节因子在良性前列腺增生以及未经治疗和激素难治性癌中的表达水平相同。然而，PIAS1和SRC1在激素难治性前列腺肿瘤中的表达显著低于（分别为P = 0.048和0.017）未经治疗的前列腺肿瘤。在临床材料中未发现共调节因子的过表达。矛盾的是，在一种LuCaP 70前列腺癌异种移植物中发现SRC1基因扩增且高表达。
结论：这些发现表明PIAS1和SRC1表达的降低可能与前列腺癌的进展有关。此外，其中一种异种移植物中SRC1的基因扩增意味着在某些肿瘤中，SRC1的基因改变可能提供生长优势。
Purpose: The androgen receptor (AR)-mediated signaling pathway seems to be essentially involved in the development and progression of prostate cancer. In vitro studies have shown that altered expression of AR coregulators may significantly modify transcriptional activity of AR, suggesting that these coregulators could also contribute to the progression of prostate cancer. Here, our goal was to assess alterations in the expression of the AR coregulators in prostate cancer in vivo.Experimental Design: The expression of 16 AR coactivators and corepressors (SRC1, beta-catenin, TIF2, PIAS1, PIASx, ARIP4, BRCA1, AIB1, AIB3, CBP, STAT1, NCoR1, AES, cyclin D1, p300, and ARA24) was measured in prostate cancer cell lines, xenografts, and clinical prostate tumor specimens by using real-time quantitative reverse transcription-PCR. In addition, gene copy number of SRC1 was analyzed by fluorescence in situ hybridization.Results: Both AR-positive and AR-negative cell lines and xenografts expressed the coregulators. Most of the coregulators studied were expressed at equal levels in benign prostatic hyperplasia and untreated and hormone-refractory carcinomas. However, the expression of PIAS1 and SRC1 was significantly (P = 0.048 and 0.017, respectively) lower in hormone-refractory prostate tumors than in untreated prostate tumors. No overexpression of the coregulators was found in the clinical material. Paradoxically, the SRC1 gene was found to be amplified and highly expressed in a LuCaP 70 prostate cancer xenograft.Conclusions: These findings suggest that the decreased expression of PIAS1 and SRC1 could be involved in the progression of prostate cancer. In addition, gene amplification of SRC1 in one of the xenografts implies that, in some tumors, genetic alteration of SRC1 may provide a growth advantage.