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与正常前列腺相比,前列腺癌中雄激素受体转录复合物的调控存在差异。

Differently regulated androgen receptor transcriptional complex in prostate cancer compared with normal prostate.

作者信息

Kinoshita Masashige, Nakagawa Toshimasa, Shimizu Akira, Katsuoka Yoji

机构信息

Department of Urology, Osaka Medical College, Takatsuki City, Osaka, Japan.

出版信息

Int J Urol. 2005 Apr;12(4):390-7. doi: 10.1111/j.1442-2042.2005.01093.x.

Abstract

BACKGROUND

The coregulators of androgen receptors (AR) influence the transcriptional activity of AR. In order to better understand the mechanism of carcinogenesis in the prostate, we investigated the relationship between AR and AR coregulators in the early stage of prostate cancer.

METHODS

mRNA was purified from 15 samples of prostate cancer and normal tissue and transcribed into cDNA. We screened eight AR coregulators for different gene expressions in prostate cancer, comparing these with normal tissue by a real-time polymerase chain reaction Syber green method, then quantified each component of the AR transcriptional complex by a real-time PCR hybri-probe method. The extent of gene expression similarity was compared by simple Pearson correlation coefficient analysis between prostate cancer and normal tissue. We applied a z-test to calculate significant differences between r-values.

RESULTS

We found that the gene expression level of FHL2 decreased in prostate cancer compared with that of normal tissue and the gene expressions of PSA, AR and SMRT were not significant. The correlation coefficient analysis revealed that strong associations were found in the pairs of AR versus SMRT, AR versus FHL2 and SMRT versus FHL2 in prostate cancer, whereas similarity was found only in the pair of AR versus FHL2 in normal tissue. No association was observed between prostate-specific antigen and other genes.

CONCLUSION

These results demonstrate that the AR-AR coregulator relationship is different between prostate cancer and normal tissue, leading to the hypothesis that the AR transcriptional complex is regulated differently between prostate cancer and normal tissue.

摘要

背景

雄激素受体(AR)的共调节因子会影响AR的转录活性。为了更好地理解前列腺癌的致癌机制,我们研究了前列腺癌早期AR与AR共调节因子之间的关系。

方法

从15份前列腺癌组织和正常组织样本中纯化mRNA并转录成cDNA。我们筛选了8种AR共调节因子在前列腺癌中的不同基因表达情况,通过实时聚合酶链反应Syber green法与正常组织进行比较,然后通过实时PCR杂交探针法定量AR转录复合物的各组分。通过简单的Pearson相关系数分析比较前列腺癌组织和正常组织之间基因表达的相似程度。我们应用z检验来计算r值之间的显著差异。

结果

我们发现与正常组织相比,FHL2在前列腺癌中的基因表达水平降低,而PSA、AR和SMRT的基因表达无显著差异。相关系数分析显示,在前列腺癌中,AR与SMRT、AR与FHL2以及SMRT与FHL2之间存在强关联,而在正常组织中仅在AR与FHL2之间发现相似性。未观察到前列腺特异性抗原与其他基因之间存在关联。

结论

这些结果表明,前列腺癌组织和正常组织中AR与AR共调节因子的关系不同,这导致了一种假设,即前列腺癌组织和正常组织中AR转录复合物的调节方式不同。

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