Diabetes causes multiple genetic alterations and downregulates expression of DNA repair genes in the prostate
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...
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| Veröffentlicht in: | Laboratory investigation 2011-09, Vol.91 (9), p.1363-1374 |
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| creator | Ye, Chunwei Li, Xiaojuan Wang, Yu Zhang, Yuying Cai, Mengyin Zhu, Baoyi Mu, Panwei Xia, Xuan Zhao, Yi Weng, Jianping Gao, Xin Wen, Xingqiao |
| description | 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. |
| doi_str_mv | 10.1038/labinvest.2011.87 |
| format | Article |
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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.</description><identifier>ISSN: 0023-6837</identifier><identifier>EISSN: 1530-0307</identifier><identifier>DOI: 10.1038/labinvest.2011.87</identifier><identifier>PMID: 21647090</identifier><identifier>CODEN: LAINAW</identifier><language>eng</language><publisher>New York: Elsevier Inc</publisher><subject>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</subject><ispartof>Laboratory investigation, 2011-09, Vol.91 (9), p.1363-1374</ispartof><rights>2011 United States & Canadian Academy of Pathology</rights><rights>United States and Canadian Academy of Pathology, Inc. 2011</rights><rights>2015 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Sep 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c528t-e0a2cc516518de3f0234d7cc5746f998a960c6fe19b7d620dbe73930ecdde9cf3</citedby><cites>FETCH-LOGICAL-c528t-e0a2cc516518de3f0234d7cc5746f998a960c6fe19b7d620dbe73930ecdde9cf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24520340$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21647090$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ye, Chunwei</creatorcontrib><creatorcontrib>Li, Xiaojuan</creatorcontrib><creatorcontrib>Wang, Yu</creatorcontrib><creatorcontrib>Zhang, Yuying</creatorcontrib><creatorcontrib>Cai, Mengyin</creatorcontrib><creatorcontrib>Zhu, Baoyi</creatorcontrib><creatorcontrib>Mu, Panwei</creatorcontrib><creatorcontrib>Xia, Xuan</creatorcontrib><creatorcontrib>Zhao, Yi</creatorcontrib><creatorcontrib>Weng, Jianping</creatorcontrib><creatorcontrib>Gao, Xin</creatorcontrib><creatorcontrib>Wen, Xingqiao</creatorcontrib><title>Diabetes causes multiple genetic alterations and downregulates expression of DNA repair genes in the prostate</title><title>Laboratory investigation</title><addtitle>Lab Invest</addtitle><addtitle>Lab Invest</addtitle><description>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.</description><subject>631/208/191/2018</subject><subject>631/337/1427</subject><subject>692/698/1864/1752</subject><subject>692/699/2743/137</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Blotting, Western</subject><subject>Body Weight</subject><subject>Cell Line</subject><subject>diabetes mellitus</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>DNA damage</subject><subject>DNA Primers</subject><subject>DNA Repair - genetics</subject><subject>Down-Regulation</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Etiopathogenesis. Screening. Investigations. 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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. 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| 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 |
| title | Diabetes causes multiple genetic alterations and downregulates expression of DNA repair genes in the prostate |
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