title: Diabetes causes multiple genetic alterations and downregulates expression of DNA repair genes in the prostate.
abstract: 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.
authors.affiliation: Department of Urology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Chunwei
authors.initials: C
authors.lastname: Ye
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mengyin
authors.initials: M
authors.lastname: Cai
authors.forename: Baoyi
authors.initials: B
authors.lastname: Zhu
authors.forename: Panwei
authors.initials: P
authors.lastname: Mu
authors.forename: Xuan
authors.initials: X
authors.lastname: Xia
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Jianping
authors.initials: J
authors.lastname: Weng
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
authors.forename: Xingqiao
authors.initials: X
authors.lastname: Wen
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D001835:Body Weight; D002460:Cell Line; D017931:DNA Primers; D004260:DNA Repair / Q000235:genetics*; D015536:Down-Regulation; D007150:Immunohistochemistry; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D017931:DNA Primers