Promoter hypomethylation contributes to the expression of MUC3A in cancer cells
MUC3A is a membrane-bound glycoprotein that is aberrantly expressed in carcinomas and is a risk factor for a poor prognosis. However, the exact mechanism of MUC3A expression has yet to be clarified. Here, we provide the first evidence that MUC3A gene expression is controlled by the CpG methylation s...
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Veröffentlicht in: | Biochemical and biophysical research communications 2010-06, Vol.397 (2), p.333-339 |
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description | MUC3A is a membrane-bound glycoprotein that is aberrantly expressed in carcinomas and is a risk factor for a poor prognosis. However, the exact mechanism of MUC3A expression has yet to be clarified. Here, we provide the first evidence that MUC3A gene expression is controlled by the CpG methylation status of the proximal promoter region. We show that the DNA methylation pattern is intimately correlated with MUC3A expression in breast, lung, pancreas and colon cancer cell lines. The DNA methylation status of 30CpG sites from −660 to +273 was mapped using MassARRAY analysis. MUC3A-negative cancer cell lines and those with low MUC3A expression (e.g., MCF-7) were highly methylated in the proximal promoter region, corresponding to 9CpG sites (−345 to −75bp), whereas MUC3A-positive cell lines (e.g., LS174T) had low methylation levels. Moreover, 5-aza-2′-deoxycytidine and trichostatin A treatment of MUC3A-negative cells or those with low MUC3A expression caused elevation of MUC3A mRNA. Our results suggest that DNA hypomethylation in the 5′-flanking region of the MUC3A gene plays an important role in MUC3A expression in carcinomas of various organs. An understanding of epigenetic changes in MUC3A may contribute to the diagnosis of carcinogenic risk and to prediction of outcome in patients with cancer. |
doi_str_mv | 10.1016/j.bbrc.2010.05.124 |
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However, the exact mechanism of MUC3A expression has yet to be clarified. Here, we provide the first evidence that MUC3A gene expression is controlled by the CpG methylation status of the proximal promoter region. We show that the DNA methylation pattern is intimately correlated with MUC3A expression in breast, lung, pancreas and colon cancer cell lines. The DNA methylation status of 30CpG sites from −660 to +273 was mapped using MassARRAY analysis. MUC3A-negative cancer cell lines and those with low MUC3A expression (e.g., MCF-7) were highly methylated in the proximal promoter region, corresponding to 9CpG sites (−345 to −75bp), whereas MUC3A-positive cell lines (e.g., LS174T) had low methylation levels. Moreover, 5-aza-2′-deoxycytidine and trichostatin A treatment of MUC3A-negative cells or those with low MUC3A expression caused elevation of MUC3A mRNA. Our results suggest that DNA hypomethylation in the 5′-flanking region of the MUC3A gene plays an important role in MUC3A expression in carcinomas of various organs. An understanding of epigenetic changes in MUC3A may contribute to the diagnosis of carcinogenic risk and to prediction of outcome in patients with cancer.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2010.05.124</identifier><identifier>PMID: 20510874</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>5' Flanking Region - genetics ; Azacitidine - analogs & derivatives ; Azacitidine - pharmacology ; Carcinoma - genetics ; Cell Line, Tumor ; DNA Methylation ; Epigenetic marker ; Gene Expression - drug effects ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; Hydroxamic Acids - pharmacology ; Hypomethylation ; MUC3A ; Mucin ; Mucin-3 - genetics ; RNA, Messenger - biosynthesis</subject><ispartof>Biochemical and biophysical research communications, 2010-06, Vol.397 (2), p.333-339</ispartof><rights>2010 Elsevier Inc.</rights><rights>Copyright (c) 2010 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c453t-9dcc69b16b3f12fe598bed8265f868d76912569472540f7edf5b933b8399d1323</citedby><cites>FETCH-LOGICAL-c453t-9dcc69b16b3f12fe598bed8265f868d76912569472540f7edf5b933b8399d1323</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2010.05.124$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20510874$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kitamoto, Sho</creatorcontrib><creatorcontrib>Yamada, Norishige</creatorcontrib><creatorcontrib>Yokoyama, Seiya</creatorcontrib><creatorcontrib>Houjou, Izumi</creatorcontrib><creatorcontrib>Higashi, Michiyo</creatorcontrib><creatorcontrib>Yonezawa, Suguru</creatorcontrib><title>Promoter hypomethylation contributes to the expression of MUC3A in cancer cells</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>MUC3A is a membrane-bound glycoprotein that is aberrantly expressed in carcinomas and is a risk factor for a poor prognosis. However, the exact mechanism of MUC3A expression has yet to be clarified. Here, we provide the first evidence that MUC3A gene expression is controlled by the CpG methylation status of the proximal promoter region. We show that the DNA methylation pattern is intimately correlated with MUC3A expression in breast, lung, pancreas and colon cancer cell lines. The DNA methylation status of 30CpG sites from −660 to +273 was mapped using MassARRAY analysis. MUC3A-negative cancer cell lines and those with low MUC3A expression (e.g., MCF-7) were highly methylated in the proximal promoter region, corresponding to 9CpG sites (−345 to −75bp), whereas MUC3A-positive cell lines (e.g., LS174T) had low methylation levels. Moreover, 5-aza-2′-deoxycytidine and trichostatin A treatment of MUC3A-negative cells or those with low MUC3A expression caused elevation of MUC3A mRNA. Our results suggest that DNA hypomethylation in the 5′-flanking region of the MUC3A gene plays an important role in MUC3A expression in carcinomas of various organs. An understanding of epigenetic changes in MUC3A may contribute to the diagnosis of carcinogenic risk and to prediction of outcome in patients with cancer.</description><subject>5' Flanking Region - genetics</subject><subject>Azacitidine - analogs & derivatives</subject><subject>Azacitidine - pharmacology</subject><subject>Carcinoma - genetics</subject><subject>Cell Line, Tumor</subject><subject>DNA Methylation</subject><subject>Epigenetic marker</subject><subject>Gene Expression - drug effects</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Silencing</subject><subject>Humans</subject><subject>Hydroxamic Acids - pharmacology</subject><subject>Hypomethylation</subject><subject>MUC3A</subject><subject>Mucin</subject><subject>Mucin-3 - genetics</subject><subject>RNA, Messenger - biosynthesis</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMFqGzEQQEVJqR2nP9BD2FtO646klXYFvQSTtAEX91BDbmKlncUyXsuV5BD_fbTY6bE9CUZvHsMj5AuFOQUqv27nxgQ7Z5AHIOaUVR_IlIKCklGorsgUAGTJFH2ekOsYtwCUVlJ9IhMGgkJTV1Oy-hX84BOGYnM6-AHT5rRrk_P7wvp9Cs4cE8Yi-SJtsMDXQ8AYx1_fFz_XC35fuEy2e5sFFne7eEM-9u0u4ufLOyPrx4ffix_lcvX9aXG_LG0leCpVZ61UhkrDe8p6FKox2DVMir6RTVdLRZmQqqqZqKCvseuFUZybhivVUc74jNydvYfg_xwxJj24OF7Q7tEfo64lY7Kuufw_ybkU2Ugzyc6kDT7GgL0-BDe04aQp6LG43uqxuB6LaxA6F89Ltxf90QzY_V15T5yBb2cAc44Xh0FH6zAX61xAm3Tn3b_8byfMkOo</recordid><startdate>20100625</startdate><enddate>20100625</enddate><creator>Kitamoto, Sho</creator><creator>Yamada, Norishige</creator><creator>Yokoyama, Seiya</creator><creator>Houjou, Izumi</creator><creator>Higashi, Michiyo</creator><creator>Yonezawa, Suguru</creator><general>Elsevier Inc</general><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>7X8</scope><scope>7TM</scope></search><sort><creationdate>20100625</creationdate><title>Promoter hypomethylation contributes to the expression of MUC3A in cancer cells</title><author>Kitamoto, Sho ; Yamada, Norishige ; Yokoyama, Seiya ; Houjou, Izumi ; Higashi, Michiyo ; Yonezawa, Suguru</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c453t-9dcc69b16b3f12fe598bed8265f868d76912569472540f7edf5b933b8399d1323</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>5' Flanking Region - genetics</topic><topic>Azacitidine - analogs & derivatives</topic><topic>Azacitidine - pharmacology</topic><topic>Carcinoma - genetics</topic><topic>Cell Line, Tumor</topic><topic>DNA Methylation</topic><topic>Epigenetic marker</topic><topic>Gene Expression - drug effects</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene Silencing</topic><topic>Humans</topic><topic>Hydroxamic Acids - pharmacology</topic><topic>Hypomethylation</topic><topic>MUC3A</topic><topic>Mucin</topic><topic>Mucin-3 - genetics</topic><topic>RNA, Messenger - biosynthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kitamoto, Sho</creatorcontrib><creatorcontrib>Yamada, Norishige</creatorcontrib><creatorcontrib>Yokoyama, Seiya</creatorcontrib><creatorcontrib>Houjou, Izumi</creatorcontrib><creatorcontrib>Higashi, Michiyo</creatorcontrib><creatorcontrib>Yonezawa, Suguru</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kitamoto, Sho</au><au>Yamada, Norishige</au><au>Yokoyama, Seiya</au><au>Houjou, Izumi</au><au>Higashi, Michiyo</au><au>Yonezawa, Suguru</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Promoter hypomethylation contributes to the expression of MUC3A in cancer cells</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2010-06-25</date><risdate>2010</risdate><volume>397</volume><issue>2</issue><spage>333</spage><epage>339</epage><pages>333-339</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>MUC3A is a membrane-bound glycoprotein that is aberrantly expressed in carcinomas and is a risk factor for a poor prognosis. 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Our results suggest that DNA hypomethylation in the 5′-flanking region of the MUC3A gene plays an important role in MUC3A expression in carcinomas of various organs. An understanding of epigenetic changes in MUC3A may contribute to the diagnosis of carcinogenic risk and to prediction of outcome in patients with cancer.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>20510874</pmid><doi>10.1016/j.bbrc.2010.05.124</doi><tpages>7</tpages></addata></record> |
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subjects | 5' Flanking Region - genetics Azacitidine - analogs & derivatives Azacitidine - pharmacology Carcinoma - genetics Cell Line, Tumor DNA Methylation Epigenetic marker Gene Expression - drug effects Gene Expression Regulation, Neoplastic Gene Silencing Humans Hydroxamic Acids - pharmacology Hypomethylation MUC3A Mucin Mucin-3 - genetics RNA, Messenger - biosynthesis |
title | Promoter hypomethylation contributes to the expression of MUC3A in cancer cells |
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