Molecular classification of doxazosin-induced alterations in the rat prostate using gene expression profiling.
Molecular classification of doxazosin-induced alterations in the rat prostate using gene expression profiling.
复制标题
使用基因表达谱对多沙唑嗪诱导的大鼠前列腺改变进行分子分类。
DOI：
10.1016/j.lfs.2005.01.004
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Latifpour,Jamshid
中科院分区：
文献类型：
--
作者：
Yono,Makoto;FosterJr,HarrisE;Shin,David;Mane,Shrikant;Latifpour,Jamshid
我们使用Affymetrix基因芯片的基因表达分析，研究了长期服用α1肾上腺素能受体(AR)拮抗剂多沙唑嗪期间发生的分子变化。大鼠皮下注射多沙唑嗪4 mg/kg/d，口服4 mg/kg/d，共12周。制备标记的cRNA，并与大鼠230A阵列进行杂交。使用SYBR Green I的实时逆转录聚合酶链式反应(RT-PCR)验证了微阵列分析确定的具有潜在生物学相关性的候选基因的基因表达水平的变化。与对照组大鼠相比，多沙唑嗪处理组大鼠的前列腺重量明显增加。基因芯片分析显示，慢性多沙唑嗪治疗引起625个基因表达水平的变化，其中39个基因与大鼠前列腺细胞死亡、坏死、生长、增殖和G蛋白信号通路有关。此外，与芯片分析一致的RT-PCR实验表明，慢性多沙唑嗪治疗后，前列腺腹侧和背侧的抗细胞凋亡介质聚集素和有丝分裂原表观调节素的mRNA表达水平分别上调。这些发现表明，长期服用多沙唑嗪会导致大鼠前列腺数百个基因的表达发生显著变化，这可能为研究α1-AR拮抗剂治疗良性前列腺增生症的长期疗效提供依据。
We investigated molecular changes that occurred during chronic administration of doxazosin, an α1-adrenoceptor (AR) antagonist, using Affymetrix GeneChip analysis of gene expression. Rats were treated with doxazosin (4 mg/kg/day subcutaneously, supplemented with 4 mg/kg/day orally) for 12 weeks. Labeled cRNA was prepared and the subsequent hybridization to rat 230A arrays was performed. The alterations in gene expression levels of candidate genes identified by microarray analysis with potential biological relevance were verified by real-time reverse transcription polymerase chain reaction (RT-PCR) using SYBR Green I. Doxazosin treated rats had significantly heavier prostates compared to control rats. Microarray analysis revealed that chronic doxazosin treatment caused changes in the expression levels of 625 genes, of which 39 were related to cell death, necrosis, growth, proliferation and G-protein signalling pathways in the rat prostate. Furthermore, RT-PCR experiments, in accord with the microarray analysis, indicated that chronic doxazosin treatment caused an up-regulation in the mRNA expression level of clusterin, an antiapoptotic mediator, and epiregulin, a mitogen, in the ventral and dorsolateral prostate, respectively. These findings, that demonstrate chronic doxazosin administration causes significant changes in the expression of several hundred genes in the rat prostate, may provide insight into the long-term efficacy of α1-AR antagonists in the treatment of benign prostatic hyperplasia.