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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The program of androgen-responsive genes in neoplastic prostate epithelium
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The program of androgen-responsive genes in neoplastic prostate epithelium

机译：肿瘤前列腺上皮中雄激素反应性基因的程序

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The human prostate gland is an important target organ of andro-genic hormones. Testosterone and dihydrotestosterone interact with the androgen receptor to regulate vital aspects of prostate growth and function including cellular proliferation, differentiation, apoptosis, metabolism, and secretory activity. Our objective in this study was to characterize the temporal program of transcription that reflects the cellular response to androgens and to identify specific androgen-regulated genes (ARGs) or gene networks that participate in these responses. We used cDNA micro-arrays representing about 20,000 distinct human genes to profile androgen-responsive transcripts in the LNCaP adenocarcinoma cell line and identified 146 genes with transcript alterations more than 3-fold. Of these, 103 encode proteins with described functional roles, and 43 represent transcripts that have yet to be characterized. Temporal gene expression profiles grouped the ARGs into four distinct cohorts. Five uncharacterized ARGs demonstrated exclusive or high expression levels in the prostate relative to other tissues studied. A search of available DNA sequence upstream of 28 ARGs identified 25 with homology to the androgen response-element consensus-binding motif. These results identify previously uncharacterized and unsuspected genes whose expression levels are directly or indirectly regulated by androgens; further, they provide a comprehensive temporal view of the transcriptional program of human androgen-responsive cells.
机译：人前列腺是雄激素的重要靶器官。睾丸激素和二氢睾丸激素与雄激素受体相互作用，调节前列腺生长和功能的重要方面，包括细胞增殖，分化，凋亡，代谢和分泌活性。我们在这项研究中的目的是表征反映细胞对雄激素的反应的转录时间程序，并鉴定参与这些反应的特定雄激素调节基因（ARG）或基因网络。我们使用代表约20,000个不同人类基因的cDNA微阵列，对LNCaP腺癌细胞系中的雄激素反应性转录物进行了分析，并鉴定了146个转录物改变超过3倍的基因。其中，103个编码具有所描述功能作用的蛋白质，43个代表尚未表征的转录本。时间基因表达谱将ARGs分为四个不同的队列。相对于研究的其他组织，五个未表征的ARGs在前列腺中表现出排他性或高表达水平。搜寻28个ARG上游的可用DNA序列，发现其中25个与雄激素反应元素共有结合基序具有同源性。这些结果确定了以前未鉴定和未怀疑的基因，其表达水平直接或间接受雄激素调节。此外，它们提供了人类雄激素反应性细胞转录程序的全面时间视图。

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