Diabetes causes multiple genetic alterations and downregulates expression of DNA repair genes in the prostate

• Published in: Laboratory investigation Vol. 91; no. 9; pp. 1363 - 1374
• Main Authors: Ye, Chunwei, Li, Xiaojuan, Wang, Yu, Zhang, Yuying, Cai, Mengyin, Zhu, Baoyi, Mu, Panwei, Xia, Xuan, Zhao, Yi, Weng, Jianping, Gao, Xin, Wen, Xingqiao
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01-09-2011; Nature Publishing Group US; Nature Publishing Group
• Subjects: 631/208/191/2018; 631/337/1427; 692/698/1864/1752; 692/699/2743/137; Animals; Base Sequence; Biological and medical sciences; Biotechnology; Blotting, Western; Body Weight; Cell Line; diabetes mellitus; Diabetes. Impaired glucose tolerance; DNA damage; DNA Primers; DNA Repair - genetics; Down-Regulation; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fundamental and applied biological sciences. Psychology; Immunohistochemistry; Investigative techniques, diagnostic techniques (general aspects); Laboratory Medicine; Male; Medical sciences; Medicine; Medicine & Public Health; microarray; Oligonucleotide Array Sequence Analysis; Organ Size; oxidative stress; Pathology; Polymerase Chain Reaction; prostate; Prostatic Neoplasms - genetics; Rats; Rats, Sprague-Dawley; research-article; microarray; diabetes mellitus; prostate; DNA damage; oxidative stress; Endocrinopathy; Biotechnology; Oxidative stress; Multiple; Diabetes mellitus; Gene expression; DNA repair; Repair gene; DNA; Clinical biology; Cause; Lesion; Urogenital system; Prostate
• ISSN: 0023-6837; 1530-0307
• DOI: 10.1038/labinvest.2011.87

The molecular impact of diabetes mellitus on prostate gland has not been elucidated. In this study, we performed a whole-genome cDNA microarray analysis using a streptozotocin-induced diabetic rat model to identify the effects of diabetes on the gene expression profiles in prostate. Our study shows that diabetes causes changes in the expression of multiple genes, particularly those related to cell proliferation and differentiation, oxidative stress, DNA damage repair, cell cycle checkpoints, angiogenesis and apoptosis. These findings were confirmed by real-time polymerase chain reaction and immunohistochemical staining using rat and human prostate tissue. We also used a cell culture model (human normal prostatic RWPE-1 cell line) to study the direct effect of high glucose. We found that high glucose caused increased intracellular oxidative stress and DNA damage, as well as downregulation of anti-oxidative enzymes and DNA damage repair genes MRE11 and XRCC3. Our findings provide important insights into understanding the pathogenesis of the diabetes-induced changes in prostate as well as identifying potential therapeutic targets for future studies.