在棕色挪威大鼠前列腺增生模型中，基因表达变化具有年龄依赖性且呈叶特异性。

Gene expression changes are age-dependent and lobe-specific in the brown Norway rat model of prostatic hyperplasia.

作者信息

Bethel Carlise R, Chaudhary Jaideep, Anway Matthew D, Brown Terry R

机构信息

Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA.

出版信息

Prostate. 2009 Jun 1;69(8):838-50. doi: 10.1002/pros.20935.

DOI:10.1002/pros.20935

PMID:19204916

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2732361/

Abstract

BACKGROUND

Benign prostatic hyperplasia (BPH) is an age-related enlargement of the prostate, characterized by increased proliferation of stromal and epithelial cells. Despite its prevalence, the etiology of BPH is unknown.

METHODS

The Brown Norway rat is a model for age-dependent, lobe-specific hyperplasia of the prostate. Histological analyses of the dorsal and lateral lobes from aged rats reveal focal areas characterized by increased numbers of luminal epithelial cells, whereas the ventral lobe is unaffected. This study examined differential gene expression by lobe and age in the Brown Norway rat prostate. The objective was to identify genes with different levels of expression in the prostate lobes from 4-month (young) and 24-month (old) animals, and to subsequently link changes in gene expression to mechanisms of prostate aging.

RESULTS

The number of age-dependent differentially expressed genes was greatest in the dorsal compared to the ventral and lateral lobes. Minimal redundancy was observed among the differentially expressed genes in the three lobes. Age-related changes in the expression levels of 14 candidate genes in the dorsal, lateral and ventral lobes were confirmed by quantitative RT-PCR. Genes that exhibited age-related differences in their expression were associated with proliferation, oxidative stress, and prostate cancer progression, including topoisomerase II alpha (Topo2a), aurora kinase B (Aurkb), stathmin 1 (Stmn1), and glutathione S-transferase pi. Immunohistochemistry for Topo2a, Aurkb, and Stmn1 confirmed age-related changes in protein localization in the lateral lobe of young and aged prostates.

CONCLUSION

These findings provide clues to the molecular events associated with aging in the prostate.

摘要

背景

良性前列腺增生（BPH）是一种与年龄相关的前列腺增大，其特征是基质和上皮细胞增殖增加。尽管其患病率很高，但BPH的病因尚不清楚。

方法

棕色挪威大鼠是前列腺年龄依赖性、叶特异性增生的模型。对老年大鼠背叶和侧叶的组织学分析显示，局部区域的腔上皮细胞数量增加，而腹叶未受影响。本研究检测了棕色挪威大鼠前列腺中叶和年龄的差异基因表达。目的是鉴定4个月（年轻）和24个月（老年）动物前列腺叶中表达水平不同的基因，并随后将基因表达变化与前列腺衰老机制联系起来。

结果

与腹叶和侧叶相比，背叶中年龄依赖性差异表达基因的数量最多。在三个叶的差异表达基因中观察到最小的冗余。通过定量RT-PCR证实了背叶、侧叶和腹叶中14个候选基因表达水平的年龄相关变化。表达呈现年龄相关差异的基因与增殖、氧化应激和前列腺癌进展相关，包括拓扑异构酶IIα（Topo2a）、极光激酶B（Aurkb）、微管相关蛋白（Stmn1）和谷胱甘肽S-转移酶pi。对Topo2a、Aurkb和Stmn1的免疫组织化学证实了年轻和老年前列腺侧叶中蛋白质定位的年龄相关变化。