Reversal of epigenetic silencing of AP-2alpha results in increased zinc uptake in DU-145 and LNCaP prostate cancer cells
Zinc accumulation is lost during prostate carcinogenesis. Recent studies reveal a strong association between prostate cancer progression and the downregulation of the zinc uptake transporters hZip1 and hZip3. The aim of this work was to assess the involvement of epigenetic processes in the disruptio...
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| Veröffentlicht in: | Carcinogenesis (New York) 2011-12, Vol.32 (12), p.1773-1781 |
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| creator | Makhov, Peter B. Golovine, Konstantin V. Kutikov, Alexander Canter, Daniel J. Rybko, Vera A. Roshchin, Dmitry A. Matveev, Vsevolod B. Uzzo, Robert G. Kolenko, Vladimir M. |
| description | Zinc accumulation is lost during prostate carcinogenesis. Recent studies reveal a strong association between prostate cancer progression and the downregulation of the zinc uptake transporters hZip1 and hZip3. The aim of this work was to assess the involvement of epigenetic processes in the disruption of zinc uptake homeostasis in prostate adenocarcinoma. In this report, we demonstrate an increase in hZip1 and hZip3 zinc transporters' expression and zinc uptake by the prostate cancer cells DU-145 and LNCaP in response to 5-aza-2′-deoxycytidine. This effect is due to demethylation of the promoter region of the activator protein (AP)-2alpha protein, which is crucial for hZip1 and hZip3 genes expression. Loss of AP-2alpha expression in DU-145 and LNCaP prostate cancer cells is due to hypermethylation of its promoter region. Similarly, we found higher AP-2alpha promoter methylation levels in clinical samples of early-stage prostate adenocarcinoma when compared with adjacent non-malignant prostate tissue. Taken together, our findings provide a better understanding of the epigenetic mechanisms that are involved in the loss of AP-2alpha protein in prostate cancer cells which lead to decreased cellular zinc uptake-a sine qua non of prostate cancer development. |
| doi_str_mv | 10.1093/carcin/bgr212 |
| format | Article |
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Recent studies reveal a strong association between prostate cancer progression and the downregulation of the zinc uptake transporters hZip1 and hZip3. The aim of this work was to assess the involvement of epigenetic processes in the disruption of zinc uptake homeostasis in prostate adenocarcinoma. In this report, we demonstrate an increase in hZip1 and hZip3 zinc transporters' expression and zinc uptake by the prostate cancer cells DU-145 and LNCaP in response to 5-aza-2′-deoxycytidine. This effect is due to demethylation of the promoter region of the activator protein (AP)-2alpha protein, which is crucial for hZip1 and hZip3 genes expression. Loss of AP-2alpha expression in DU-145 and LNCaP prostate cancer cells is due to hypermethylation of its promoter region. Similarly, we found higher AP-2alpha promoter methylation levels in clinical samples of early-stage prostate adenocarcinoma when compared with adjacent non-malignant prostate tissue. Taken together, our findings provide a better understanding of the epigenetic mechanisms that are involved in the loss of AP-2alpha protein in prostate cancer cells which lead to decreased cellular zinc uptake-a sine qua non of prostate cancer development.</description><identifier>ISSN: 0143-3334</identifier><identifier>EISSN: 1460-2180</identifier><identifier>DOI: 10.1093/carcin/bgr212</identifier><identifier>PMID: 21940908</identifier><identifier>CODEN: CRNGDP</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Azacitidine - analogs & derivatives ; Azacitidine - pharmacology ; Base Sequence ; Cancer Biology ; Cation Transport Proteins - metabolism ; Cell Line, Tumor ; Chromatin Immunoprecipitation ; DNA Methylation ; DNA Primers ; Epigenesis, Genetic ; Gene Silencing ; Humans ; Male ; Promoter Regions, Genetic ; Prostatic Neoplasms - genetics ; Prostatic Neoplasms - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription Factor AP-2 - genetics ; Transcription Factor AP-2 - physiology ; Transcription, Genetic ; Zinc - metabolism</subject><ispartof>Carcinogenesis (New York), 2011-12, Vol.32 (12), p.1773-1781</ispartof><rights>The Author 2011. 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Recent studies reveal a strong association between prostate cancer progression and the downregulation of the zinc uptake transporters hZip1 and hZip3. The aim of this work was to assess the involvement of epigenetic processes in the disruption of zinc uptake homeostasis in prostate adenocarcinoma. In this report, we demonstrate an increase in hZip1 and hZip3 zinc transporters' expression and zinc uptake by the prostate cancer cells DU-145 and LNCaP in response to 5-aza-2′-deoxycytidine. This effect is due to demethylation of the promoter region of the activator protein (AP)-2alpha protein, which is crucial for hZip1 and hZip3 genes expression. Loss of AP-2alpha expression in DU-145 and LNCaP prostate cancer cells is due to hypermethylation of its promoter region. Similarly, we found higher AP-2alpha promoter methylation levels in clinical samples of early-stage prostate adenocarcinoma when compared with adjacent non-malignant prostate tissue. Taken together, our findings provide a better understanding of the epigenetic mechanisms that are involved in the loss of AP-2alpha protein in prostate cancer cells which lead to decreased cellular zinc uptake-a sine qua non of prostate cancer development.</description><subject>Azacitidine - analogs & derivatives</subject><subject>Azacitidine - pharmacology</subject><subject>Base Sequence</subject><subject>Cancer Biology</subject><subject>Cation Transport Proteins - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Chromatin Immunoprecipitation</subject><subject>DNA Methylation</subject><subject>DNA Primers</subject><subject>Epigenesis, Genetic</subject><subject>Gene Silencing</subject><subject>Humans</subject><subject>Male</subject><subject>Promoter Regions, Genetic</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Prostatic Neoplasms - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Transcription Factor AP-2 - genetics</subject><subject>Transcription Factor AP-2 - physiology</subject><subject>Transcription, Genetic</subject><subject>Zinc - metabolism</subject><issn>0143-3334</issn><issn>1460-2180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1v1DAQxS0EokvhyBX5gsQl1F9JnAtStUBBWkGF6Nma2JOtwesEO6mAv75e7dLCCcmSLc9P783MI-Q5Z6856-SZhWR9POu3SXDxgKy4algluGYPyYpxJSsppTohT3L-xhhvZN09JieCd4p1TK_Izy94gylDoONAcfJbjDh7S7MPGIvwdv9_flkJCNM10IR5CXOmPpZjE0JGR3-XJ12mGb7jvvD2quKqphAd3XxawyWd0phnmJFaiBYTtRhCfkoeDRAyPjvep-Tq_buv6w_V5vPFx_X5prJKi7nqHetlr3UzYNu30AullWhx6OrBCd06pRha13SsbpVreAPY2dopq-uWg2ZSnpI3B91p6XfoLMY5QTBT8jtIv8wI3vxbif7abMcbI4VgDWuLwKujQBp_LJhns_N5PwJEHJdsysK1bHXdsIJWB9SWiXPC4c6GM7NPyxzSMoe0Cv_i797u6D_xFODlEYBsIQypLNDne04VXyX0fY_jMv3H8xYtyK33</recordid><startdate>20111201</startdate><enddate>20111201</enddate><creator>Makhov, Peter B.</creator><creator>Golovine, Konstantin V.</creator><creator>Kutikov, Alexander</creator><creator>Canter, Daniel J.</creator><creator>Rybko, Vera A.</creator><creator>Roshchin, Dmitry A.</creator><creator>Matveev, Vsevolod B.</creator><creator>Uzzo, Robert G.</creator><creator>Kolenko, Vladimir M.</creator><general>Oxford University Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>7U7</scope><scope>C1K</scope><scope>5PM</scope></search><sort><creationdate>20111201</creationdate><title>Reversal of epigenetic silencing of AP-2alpha results in increased zinc uptake in DU-145 and LNCaP prostate cancer cells</title><author>Makhov, Peter B. ; Golovine, Konstantin V. ; Kutikov, Alexander ; Canter, Daniel J. ; Rybko, Vera A. ; Roshchin, Dmitry A. ; Matveev, Vsevolod B. ; Uzzo, Robert G. ; Kolenko, Vladimir M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c482t-bd0b3b886fe7b7ab248427ef95fd287d440ecd690574d616ae9c5d4c8571a8033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Azacitidine - analogs & derivatives</topic><topic>Azacitidine - pharmacology</topic><topic>Base Sequence</topic><topic>Cancer Biology</topic><topic>Cation Transport Proteins - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Chromatin Immunoprecipitation</topic><topic>DNA Methylation</topic><topic>DNA Primers</topic><topic>Epigenesis, Genetic</topic><topic>Gene Silencing</topic><topic>Humans</topic><topic>Male</topic><topic>Promoter Regions, Genetic</topic><topic>Prostatic Neoplasms - genetics</topic><topic>Prostatic Neoplasms - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Transcription Factor AP-2 - genetics</topic><topic>Transcription Factor AP-2 - physiology</topic><topic>Transcription, Genetic</topic><topic>Zinc - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Makhov, Peter B.</creatorcontrib><creatorcontrib>Golovine, Konstantin V.</creatorcontrib><creatorcontrib>Kutikov, Alexander</creatorcontrib><creatorcontrib>Canter, Daniel J.</creatorcontrib><creatorcontrib>Rybko, Vera A.</creatorcontrib><creatorcontrib>Roshchin, Dmitry A.</creatorcontrib><creatorcontrib>Matveev, Vsevolod B.</creatorcontrib><creatorcontrib>Uzzo, Robert G.</creatorcontrib><creatorcontrib>Kolenko, Vladimir M.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Carcinogenesis (New York)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Makhov, Peter B.</au><au>Golovine, Konstantin V.</au><au>Kutikov, Alexander</au><au>Canter, Daniel J.</au><au>Rybko, Vera A.</au><au>Roshchin, Dmitry A.</au><au>Matveev, Vsevolod B.</au><au>Uzzo, Robert G.</au><au>Kolenko, Vladimir M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reversal of epigenetic silencing of AP-2alpha results in increased zinc uptake in DU-145 and LNCaP prostate cancer cells</atitle><jtitle>Carcinogenesis (New York)</jtitle><addtitle>Carcinogenesis</addtitle><date>2011-12-01</date><risdate>2011</risdate><volume>32</volume><issue>12</issue><spage>1773</spage><epage>1781</epage><pages>1773-1781</pages><issn>0143-3334</issn><eissn>1460-2180</eissn><coden>CRNGDP</coden><abstract>Zinc accumulation is lost during prostate carcinogenesis. Recent studies reveal a strong association between prostate cancer progression and the downregulation of the zinc uptake transporters hZip1 and hZip3. The aim of this work was to assess the involvement of epigenetic processes in the disruption of zinc uptake homeostasis in prostate adenocarcinoma. In this report, we demonstrate an increase in hZip1 and hZip3 zinc transporters' expression and zinc uptake by the prostate cancer cells DU-145 and LNCaP in response to 5-aza-2′-deoxycytidine. This effect is due to demethylation of the promoter region of the activator protein (AP)-2alpha protein, which is crucial for hZip1 and hZip3 genes expression. Loss of AP-2alpha expression in DU-145 and LNCaP prostate cancer cells is due to hypermethylation of its promoter region. Similarly, we found higher AP-2alpha promoter methylation levels in clinical samples of early-stage prostate adenocarcinoma when compared with adjacent non-malignant prostate tissue. Taken together, our findings provide a better understanding of the epigenetic mechanisms that are involved in the loss of AP-2alpha protein in prostate cancer cells which lead to decreased cellular zinc uptake-a sine qua non of prostate cancer development.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>21940908</pmid><doi>10.1093/carcin/bgr212</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | Azacitidine - analogs & derivatives Azacitidine - pharmacology Base Sequence Cancer Biology Cation Transport Proteins - metabolism Cell Line, Tumor Chromatin Immunoprecipitation DNA Methylation DNA Primers Epigenesis, Genetic Gene Silencing Humans Male Promoter Regions, Genetic Prostatic Neoplasms - genetics Prostatic Neoplasms - metabolism Reverse Transcriptase Polymerase Chain Reaction Transcription Factor AP-2 - genetics Transcription Factor AP-2 - physiology Transcription, Genetic Zinc - metabolism |
| title | Reversal of epigenetic silencing of AP-2alpha results in increased zinc uptake in DU-145 and LNCaP prostate cancer cells |
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