Epigenetic status and aberrant expression of the maspin gene in human hepato-biliary tract carcinomas
We examined expression of maspin and the epigenetic status of its gene in 40 primary hepato-biliary tract carcinomas and 11 cell lines originating from hepato-pancreatico-biliary tract carcinomas. Aberrant maspin expression was frequently observed immunohistochemically in biliary tract carcinomas (2...
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| Veröffentlicht in: | Laboratory investigation 2005-02, Vol.85 (2), p.214-224 |
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| creator | Fujisawa, Kentaro Maesawa, Chihaya Sato, Ryo Wada, Kei Ogasawara, Satoshi Akiyama, Yuji Takeda, Masaru Fujita, Tomohiro Otsuka, Koki Higuchi, Taro Suzuki, Kazuyuki Saito, Kazuyoshi Masuda, Tomoyuki |
| description | We examined expression of maspin and the epigenetic status of its gene in 40 primary hepato-biliary tract carcinomas and 11 cell lines originating from hepato-pancreatico-biliary tract carcinomas. Aberrant maspin expression was frequently observed immunohistochemically in biliary tract carcinomas (22/25, 88%) but not in hepatocellular carcinomas (HCCs) (0/15, 0%). Aberrant maspin expression by five pancreatico-biliary tract carcinoma cell lines was closely associated with demethylation at the maspin promoter. Five of six HCC cell lines were maspin-negative and exhibited extensive hypomethylation and hypoacetylation at the maspin promoter. Treatment with 5-aza-2'-deoxycytidine did not activate maspin expression in these five maspin-negative HCC cell lines, whereas treatment with Trichostatin A (TSA) activated maspin expression in two of them. Treatment with TSA increased histone acetylation in some HCC cell lines. These results suggest that aberrant maspin expression in biliary tract carcinomas is closely associated with demethylation at the promoter region, but that some HCC cell lines additionally require histone acetylation. In addition, the fact that maspin-negative HCC cell lines remain after treatment with TSA suggests the existence of other repressive factors controlling maspin expression. |
| doi_str_mv | 10.1038/labinvest.3700214 |
| format | Article |
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Aberrant maspin expression was frequently observed immunohistochemically in biliary tract carcinomas (22/25, 88%) but not in hepatocellular carcinomas (HCCs) (0/15, 0%). Aberrant maspin expression by five pancreatico-biliary tract carcinoma cell lines was closely associated with demethylation at the maspin promoter. Five of six HCC cell lines were maspin-negative and exhibited extensive hypomethylation and hypoacetylation at the maspin promoter. Treatment with 5-aza-2'-deoxycytidine did not activate maspin expression in these five maspin-negative HCC cell lines, whereas treatment with Trichostatin A (TSA) activated maspin expression in two of them. Treatment with TSA increased histone acetylation in some HCC cell lines. These results suggest that aberrant maspin expression in biliary tract carcinomas is closely associated with demethylation at the promoter region, but that some HCC cell lines additionally require histone acetylation. In addition, the fact that maspin-negative HCC cell lines remain after treatment with TSA suggests the existence of other repressive factors controlling maspin expression.</description><identifier>ISSN: 0023-6837</identifier><identifier>EISSN: 1530-0307</identifier><identifier>DOI: 10.1038/labinvest.3700214</identifier><identifier>PMID: 15608662</identifier><identifier>CODEN: LAINAW</identifier><language>eng</language><publisher>New York: Elsevier Inc</publisher><subject>Acetylation ; Bile Duct Neoplasms - genetics ; Bile Duct Neoplasms - metabolism ; Biological and medical sciences ; Biotechnology ; Carcinoma - genetics ; Carcinoma - metabolism ; Cell Line, Tumor ; Chromatin - metabolism ; DNA Methylation ; Epigenesis, Genetic ; Female ; Fundamental and applied biological sciences. Psychology ; Genes, Tumor Suppressor ; hepato-biliary tract carcinoma ; histone acetylation ; Humans ; Hydroxamic Acids - pharmacology ; Immunohistochemistry ; Investigative techniques, diagnostic techniques (general aspects) ; Laboratory Medicine ; Liver Neoplasms - genetics ; Liver Neoplasms - metabolism ; Male ; maspin ; Medical sciences ; Medicine ; Medicine & Public Health ; Middle Aged ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - metabolism ; Pathology ; Precipitin Tests ; Promoter Regions, Genetic ; Protein Synthesis Inhibitors - pharmacology ; Proteins - genetics ; Proteins - metabolism ; research-article ; RNA, Messenger - metabolism ; Sequence Analysis, DNA ; Serpins - genetics ; Serpins - metabolism ; tumor suppressor gene</subject><ispartof>Laboratory investigation, 2005-02, Vol.85 (2), p.214-224</ispartof><rights>2005 United States & Canadian Academy of Pathology</rights><rights>United States and Canadian Academy of Pathology, Inc. 2005</rights><rights>2006 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Feb 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c560t-5d40173102b5b8058d9d555526e1c47d475ee204cac3c654e4aa6b313db5c8e03</citedby><cites>FETCH-LOGICAL-c560t-5d40173102b5b8058d9d555526e1c47d475ee204cac3c654e4aa6b313db5c8e03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17572954$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15608662$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fujisawa, Kentaro</creatorcontrib><creatorcontrib>Maesawa, Chihaya</creatorcontrib><creatorcontrib>Sato, Ryo</creatorcontrib><creatorcontrib>Wada, Kei</creatorcontrib><creatorcontrib>Ogasawara, Satoshi</creatorcontrib><creatorcontrib>Akiyama, Yuji</creatorcontrib><creatorcontrib>Takeda, Masaru</creatorcontrib><creatorcontrib>Fujita, Tomohiro</creatorcontrib><creatorcontrib>Otsuka, Koki</creatorcontrib><creatorcontrib>Higuchi, Taro</creatorcontrib><creatorcontrib>Suzuki, Kazuyuki</creatorcontrib><creatorcontrib>Saito, Kazuyoshi</creatorcontrib><creatorcontrib>Masuda, Tomoyuki</creatorcontrib><title>Epigenetic status and aberrant expression of the maspin gene in human hepato-biliary tract carcinomas</title><title>Laboratory investigation</title><addtitle>Lab Invest</addtitle><addtitle>Lab Invest</addtitle><description>We examined expression of maspin and the epigenetic status of its gene in 40 primary hepato-biliary tract carcinomas and 11 cell lines originating from hepato-pancreatico-biliary tract carcinomas. Aberrant maspin expression was frequently observed immunohistochemically in biliary tract carcinomas (22/25, 88%) but not in hepatocellular carcinomas (HCCs) (0/15, 0%). Aberrant maspin expression by five pancreatico-biliary tract carcinoma cell lines was closely associated with demethylation at the maspin promoter. Five of six HCC cell lines were maspin-negative and exhibited extensive hypomethylation and hypoacetylation at the maspin promoter. Treatment with 5-aza-2'-deoxycytidine did not activate maspin expression in these five maspin-negative HCC cell lines, whereas treatment with Trichostatin A (TSA) activated maspin expression in two of them. Treatment with TSA increased histone acetylation in some HCC cell lines. These results suggest that aberrant maspin expression in biliary tract carcinomas is closely associated with demethylation at the promoter region, but that some HCC cell lines additionally require histone acetylation. In addition, the fact that maspin-negative HCC cell lines remain after treatment with TSA suggests the existence of other repressive factors controlling maspin expression.</description><subject>Acetylation</subject><subject>Bile Duct Neoplasms - genetics</subject><subject>Bile Duct Neoplasms - metabolism</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Carcinoma - genetics</subject><subject>Carcinoma - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Chromatin - metabolism</subject><subject>DNA Methylation</subject><subject>Epigenesis, Genetic</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genes, Tumor Suppressor</subject><subject>hepato-biliary tract carcinoma</subject><subject>histone acetylation</subject><subject>Humans</subject><subject>Hydroxamic Acids - pharmacology</subject><subject>Immunohistochemistry</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Laboratory Medicine</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - metabolism</subject><subject>Male</subject><subject>maspin</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Pathology</subject><subject>Precipitin Tests</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Synthesis Inhibitors - pharmacology</subject><subject>Proteins - genetics</subject><subject>Proteins - metabolism</subject><subject>research-article</subject><subject>RNA, Messenger - metabolism</subject><subject>Sequence Analysis, DNA</subject><subject>Serpins - genetics</subject><subject>Serpins - metabolism</subject><subject>tumor suppressor gene</subject><issn>0023-6837</issn><issn>1530-0307</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kU9rFTEUxYNY7OvTD-BGgtDupuZ_priS0qpQ6EbXIZPc16bMJGOSKfrtzeMNPnDRLHIh-Z2bk3MRek_JJSW8_zTaIcRnKPWSa0IYFa_QhkpOOsKJfo027Yx3quf6FJ2V8kQIFULJN-iUSkV6pdgGwc0cHiBCDQ6XautSsI0e2wFytrFi-D1nKCWkiNMO10fAky1ziHgvwq0-LpNtO8y2pm4IY7D5D67ZuoqdzS7E1ARv0cnOjgXerXWLft7e_Lj-1t3df_1-_eWuc81Q7aQXhGpOCRvk0BPZ-ysv22IKqBPaCy0BGBHOOu6UFCCsVQOn3A_S9UD4Fl0c-s45_VpaMGYKxcE42ghpKUZpQXlP9uDH_8CntOTYvBnGCGvZNB9bRA-Qy6mUDDsz5zC1_xlKzH4A5t8AzDqApvmwNl6GCfxRsSbegPMVsMXZcddSdqEcOS01u5L7RuzAlXYVHyAfHb70-ueDCFrIz6GJigsQHfiQwVXjU3hB_RfBcLZs</recordid><startdate>20050201</startdate><enddate>20050201</enddate><creator>Fujisawa, Kentaro</creator><creator>Maesawa, Chihaya</creator><creator>Sato, Ryo</creator><creator>Wada, Kei</creator><creator>Ogasawara, Satoshi</creator><creator>Akiyama, Yuji</creator><creator>Takeda, Masaru</creator><creator>Fujita, Tomohiro</creator><creator>Otsuka, Koki</creator><creator>Higuchi, Taro</creator><creator>Suzuki, Kazuyuki</creator><creator>Saito, Kazuyoshi</creator><creator>Masuda, Tomoyuki</creator><general>Elsevier Inc</general><general>Nature Publishing Group US</general><general>Nature Publishing</general><general>Nature Publishing Group</general><scope>6I.</scope><scope>AAFTH</scope><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>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20050201</creationdate><title>Epigenetic status and aberrant expression of the maspin gene in human hepato-biliary tract carcinomas</title><author>Fujisawa, Kentaro ; Maesawa, Chihaya ; Sato, Ryo ; Wada, Kei ; Ogasawara, Satoshi ; Akiyama, Yuji ; Takeda, Masaru ; Fujita, Tomohiro ; Otsuka, Koki ; Higuchi, Taro ; Suzuki, Kazuyuki ; Saito, Kazuyoshi ; Masuda, Tomoyuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c560t-5d40173102b5b8058d9d555526e1c47d475ee204cac3c654e4aa6b313db5c8e03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Acetylation</topic><topic>Bile Duct Neoplasms - genetics</topic><topic>Bile Duct Neoplasms - metabolism</topic><topic>Biological and medical sciences</topic><topic>Biotechnology</topic><topic>Carcinoma - genetics</topic><topic>Carcinoma - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Chromatin - metabolism</topic><topic>DNA Methylation</topic><topic>Epigenesis, Genetic</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genes, Tumor Suppressor</topic><topic>hepato-biliary tract carcinoma</topic><topic>histone acetylation</topic><topic>Humans</topic><topic>Hydroxamic Acids - pharmacology</topic><topic>Immunohistochemistry</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Laboratory Medicine</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - metabolism</topic><topic>Male</topic><topic>maspin</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Pathology</topic><topic>Precipitin Tests</topic><topic>Promoter Regions, Genetic</topic><topic>Protein Synthesis Inhibitors - pharmacology</topic><topic>Proteins - genetics</topic><topic>Proteins - metabolism</topic><topic>research-article</topic><topic>RNA, Messenger - metabolism</topic><topic>Sequence Analysis, DNA</topic><topic>Serpins - 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Aberrant maspin expression was frequently observed immunohistochemically in biliary tract carcinomas (22/25, 88%) but not in hepatocellular carcinomas (HCCs) (0/15, 0%). Aberrant maspin expression by five pancreatico-biliary tract carcinoma cell lines was closely associated with demethylation at the maspin promoter. Five of six HCC cell lines were maspin-negative and exhibited extensive hypomethylation and hypoacetylation at the maspin promoter. Treatment with 5-aza-2'-deoxycytidine did not activate maspin expression in these five maspin-negative HCC cell lines, whereas treatment with Trichostatin A (TSA) activated maspin expression in two of them. Treatment with TSA increased histone acetylation in some HCC cell lines. These results suggest that aberrant maspin expression in biliary tract carcinomas is closely associated with demethylation at the promoter region, but that some HCC cell lines additionally require histone acetylation. In addition, the fact that maspin-negative HCC cell lines remain after treatment with TSA suggests the existence of other repressive factors controlling maspin expression.</abstract><cop>New York</cop><pub>Elsevier Inc</pub><pmid>15608662</pmid><doi>10.1038/labinvest.3700214</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acetylation Bile Duct Neoplasms - genetics Bile Duct Neoplasms - metabolism Biological and medical sciences Biotechnology Carcinoma - genetics Carcinoma - metabolism Cell Line, Tumor Chromatin - metabolism DNA Methylation Epigenesis, Genetic Female Fundamental and applied biological sciences. Psychology Genes, Tumor Suppressor hepato-biliary tract carcinoma histone acetylation Humans Hydroxamic Acids - pharmacology Immunohistochemistry Investigative techniques, diagnostic techniques (general aspects) Laboratory Medicine Liver Neoplasms - genetics Liver Neoplasms - metabolism Male maspin Medical sciences Medicine Medicine & Public Health Middle Aged Pancreatic Neoplasms - genetics Pancreatic Neoplasms - metabolism Pathology Precipitin Tests Promoter Regions, Genetic Protein Synthesis Inhibitors - pharmacology Proteins - genetics Proteins - metabolism research-article RNA, Messenger - metabolism Sequence Analysis, DNA Serpins - genetics Serpins - metabolism tumor suppressor gene |
| title | Epigenetic status and aberrant expression of the maspin gene in human hepato-biliary tract carcinomas |
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