Gene expression changes are age-dependent and lobe-specificin the Brown Norway rat model of prostatic hyperplasia

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 Norwayrat prostate. Theobjective wasto 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 RTPCR. 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. © 2009 Wiley-Liss, Inc.