Dhanasekaran Saravana Mohan, Dash Atreya, Yu Jianjun, Maine Ira P, Laxman Bharathi, Tomlins Scott A, Creighton Chad J, Menon Anjana, Rubin Mark A, Chinnaiyan Arul M
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602, USA.
FASEB J. 2005 Feb;19(2):243-5. doi: 10.1096/fj.04-2415fje. Epub 2004 Nov 17.
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.
睾酮的分泌在青春期激增，促使前列腺大量生长和结构重塑，此后这种腺体结构在成年期得以维持。良性前列腺增生（BPH）和前列腺腺癌（PCA）是成年期的常见疾病，没有雄激素时不会发生。我们的目标是深入了解青春期前列腺的基因表达变化，青春期是前列腺发育中依赖雄激素的关键阶段。了解雄激素在正常前列腺发育中的作用，可能有助于更深入了解雄激素与前列腺疾病的关系。从青春期和成年年龄组的尸体器官捐献者获取良性前列腺组织，使用20,000个元件的cDNA微阵列进行分析。对微阵列数据的统计分析确定了375个在青春期前列腺中相对于成年前列腺差异表达的基因，包括Nkx3.1、TMEPAI、TGFBR3、FASN、ANKH、TGFBR2、FAAH、S100P、HoxB13、纤连蛋白和TSC2等基因。青春期和BPH表达谱的比较揭示了两组之间具有相同表达模式的一组基因。此外，我们观察到该列表中的几个基因先前已被证明受雄激素调节，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，包括肿瘤坏死因子-α诱导的脂肪相关蛋白在内的一组基因中存在雄激素反应元件，该蛋白被发现可被雄激素诱导。总之，这是第一份全面描述人类前列腺青春期发生的分子事件的报告，并提供了一组可能是青春期雄激素作用潜在体内靶点的基因。
