Premium
Molecular classification of benign prostatic hyperplasia: A gene expression profiling study in a rat model
Author(s) -
Hata Junya,
Satoh Yuichi,
Akaihata Hidenori,
Hiraki Hiroyuki,
Ogawa Soichiro,
Haga Nobuhiro,
Ishibashi Kei,
Aikawa Ken,
Kojima Yoshiyuki
Publication year - 2016
Publication title -
international journal of urology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.172
H-Index - 67
eISSN - 1442-2042
pISSN - 0919-8172
DOI - 10.1111/iju.13106
Subject(s) - hyperplasia , prostate , gene expression profiling , microarray , medicine , microarray analysis techniques , gene , gene expression , downregulation and upregulation , cancer research , biology , pathology , endocrinology , andrology , genetics , cancer
Objectives To characterize the molecular features of benign prostatic hyperplasia by carrying out a gene expression profiling analysis in a rat model. Methods Fetal urogenital sinus isolated from 20‐day‐old male rat embryo was implanted into a pubertal male rat ventral prostate. The implanted urogenital sinus grew time‐dependently, and the pathological findings at 3 weeks after implantation showed epithelial hyperplasia as well as stromal hyperplasia. Whole‐genome oligonucleotide microarray analysis utilizing approximately 30 000 oligonucleotide probes was carried out using prostate specimens during the prostate growth process (3 weeks after implantation). Results Microarray analyses showed 926 upregulated (>2‐fold change, P < 0.01) and 3217 downregulated genes (<0.5‐fold change, P < 0.01) in benign prostatic hyperplasia specimens compared with normal prostate. Gene ontology analyses of upregulated genes showed predominant genetic themes of involvement in development (162 genes, P = 2.01 × 10 −4 ), response to stimulus (163 genes, P = 7.37 × 10 −13 ) and growth (32 genes, P = 1.93 × 10 −5 ). When we used both normal prostate and non‐transplanted urogenital sinuses as controls to identify benign prostatic hyperplasia‐specific genes, 507 and 406 genes were upregulated and downregulated, respectively. Functional network and pathway analyses showed that genes associated with apoptosis modulation by heat shock protein 70, interleukin‐1, interleukin‐2 and interleukin‐5 signaling pathways, KIT signaling pathway, and secretin‐like G‐protein‐coupled receptors, class B, were relatively activated during the growth process in the benign prostatic hyperplasia specimens. In contrast, genes associated with cholesterol biosynthesis were relatively inactivated. Conclusion Our microarray analyses of the benign prostatic hyperplasia model rat might aid in clarifying the molecular mechanism of benign prostatic hyperplasia progression, and identifying molecular targets for benign prostatic hyperplasia treatment.