Molecular profiling of human prostate tissues: insights into gene expression patterns of prostate development during puberty
Molecular profiling of human prostate tissues: insights into gene expression patterns of prostate development during puberty
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DOI：
10.1096/fj.04-2415fje
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发表时间：
2004-11-01
期刊：
影响因子：
4.8
通讯作者：
Chinnaiyan, AM
中科院分区：
文献类型：
--
作者：
Dhanasekaran, SM;Dash, A;Chinnaiyan, AM
在青春期，睾丸激素的产生激增，并协调前列腺的大量生长和重组，这种腺体结构在成年后一直保持着。良性前列腺增生（BPH）和前列腺腺癌（PCA）是成年人常见的疾病，在缺乏雄激素的情况下不会发展。我们的目标是深入了解青春期前列腺的基因表达变化，这是前列腺发育中依赖雄激素的关键时刻。了解雄激素在正常前列腺发育中的作用，可以更好地了解雄激素在前列腺疾病中的作用。从青春期和成年年龄的尸体器官供体中获取良性前列腺组织，并使用20,000元素cDNA微阵列进行分析。通过对微阵列数据的统计分析，发现375个基因在青春期前列腺中与成人前列腺存在差异表达，包括Nkx3.1、TMEPAI、TGFBR3、FASN、ANKH、TGFBR2、FAAH、S100P、HoxB13、纤维连接蛋白、TSC2等基因。青春期和BPH表达谱的比较揭示了两组之间共享表达模式的基因子集。此外，我们观察到，这个列表中的几个基因先前被证明是受雄激素调节的，因此也可能是青春期人类前列腺中雄激素作用的潜在体内靶点。启动子搜索显示雄激素应答元件存在于一组基因中，包括肿瘤坏死因子- α诱导的脂肪相关蛋白，该蛋白被发现是由雄激素诱导的。综上所述，这是第一份提供青春期人类前列腺发生的分子事件的全面观点的报告，并提供了一组基因，这些基因可能是青春期雄激素作用的潜在体内靶点。
Testosterone production surges during puberty and orchestrates massive growth and reorganization of the prostate gland, and this glandular architecture is maintained thereafter throughout adulthood. Benign prostatic hyperplasia (BPH) and prostate adenocarcinoma (PCA) are common diseases in adulthood that do not develop in the absence of androgens. Our objective was to gain insight into gene expression changes of the prostate gland at puberty, a crucial juncture in prostate development that is androgen dependent. Understanding the role played by androgens in normal prostate development may provide greater insight into androgen involvement in prostatic diseases. Benign prostate tissues obtained from pubertal and adult age group cadaveric organ donors were harvested and profiled using 20,000 element cDNA microarrays. Statistical analysis of the microarray data identified 375 genes that were differentially expressed in pubertal prostates relative to adult prostates including genes such as Nkx3.1, TMEPAI, TGFBR3, FASN, ANKH, TGFBR2, FAAH, S100P, HoxB13, fibronectin, and TSC2 among others. Comparisons of pubertal and BPH expression profiles revealed a subset of genes that shared the expression pattern between the two groups. In addition, we observed that several genes from this list were previously demonstrated to be regulated by androgen and hence could also be potential in vivo targets of androgen action in the pubertal human prostate. Promoter searches revealed the presence of androgen response elements in a cohort of genes including tumor necrosis factor-alpha induced adipose related protein, which was found to be induced by androgen. In summary, this is the first report that provides a comprehensive view of the molecular events that occur during puberty in the human prostate and provides a cohort of genes that could be potential in vivo targets of androgenic action during puberty.