Involvement of the Ets-1 gene in overexpression of matrilysin in human hepatocellular carcinoma
Although matrix metalloproteinases (MMPs) are thought to be involved in the invasion and metastasis of a variety of malignant tumors, including human hepatocellular carcinoma (HCC), the mechanisms for the expression of MMPs in HCC are not known. To understand the mechanism(s) of MMP expression, the...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2000-11, Vol.60 (22), p.6519-6525 |
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| creator | OZAKI, Iwata MIZUTA, Toshihiko GANG ZHAO YOTSUMOTO, Hiroaki HARA, Toshiya KAJIHARA, Susumu HISATOMI, Akitaka SAKAI, Takahiro YAMAMOTO, Kyosuke |
| description | Although matrix metalloproteinases (MMPs) are thought to be involved in the invasion and metastasis of a variety of malignant tumors, including human hepatocellular carcinoma (HCC), the mechanisms for the expression of MMPs in HCC are not known. To understand the mechanism(s) of MMP expression, the expression of matrilysin (MMP-7) and several genes of the Ets transcription factor family was investigated in human HCC and hepatoma-derived cell lines. The role of Ets-1 gene expression in HCC was also studied. Analysis by semiquantitative reverse transcription-PCR revealed that MMP-7 and Ets-1 are overexpressed and closely associated in HCC. To clarify the role of Ets-1, hepatoma cells were transduced with human Ets-1 or targeted with the Ets-1-specific antisense oligonucleotides. Cells stably transduced with the Ets-1 gene showed increased MMP-7 expression compared to parental and mock-transfected cells. Cells targeted with Ets-1-specific antisense oligonucleotides showed reduced expression of MMP-7. Cotransfection of cells with a MMP-7 promoter-reporter gene plasmid and an Ets-1 expression vector yielded an increase in MMP-7 promoter activity in an Ets-1-responsive element-dependent manner. Taken together, these data suggested that the Ets-1 oncogene is up-regulated and involved in the overexpression of MMP-7 in human HCC and may contribute to the progression of HCC. |
| format | Article |
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To understand the mechanism(s) of MMP expression, the expression of matrilysin (MMP-7) and several genes of the Ets transcription factor family was investigated in human HCC and hepatoma-derived cell lines. The role of Ets-1 gene expression in HCC was also studied. Analysis by semiquantitative reverse transcription-PCR revealed that MMP-7 and Ets-1 are overexpressed and closely associated in HCC. To clarify the role of Ets-1, hepatoma cells were transduced with human Ets-1 or targeted with the Ets-1-specific antisense oligonucleotides. Cells stably transduced with the Ets-1 gene showed increased MMP-7 expression compared to parental and mock-transfected cells. Cells targeted with Ets-1-specific antisense oligonucleotides showed reduced expression of MMP-7. Cotransfection of cells with a MMP-7 promoter-reporter gene plasmid and an Ets-1 expression vector yielded an increase in MMP-7 promoter activity in an Ets-1-responsive element-dependent manner. Taken together, these data suggested that the Ets-1 oncogene is up-regulated and involved in the overexpression of MMP-7 in human HCC and may contribute to the progression of HCC.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>PMID: 11103822</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Aged ; Biological and medical sciences ; Carcinoma, Hepatocellular - enzymology ; Carcinoma, Hepatocellular - genetics ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Down-Regulation ; Ets-1 gene ; Female ; Fundamental and applied biological sciences. Psychology ; Gastroenterology. Liver. Pancreas. Abdomen ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Humans ; Liver Neoplasms - enzymology ; Liver Neoplasms - genetics ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Matrix Metalloproteinase 7 - biosynthesis ; Matrix Metalloproteinase 7 - genetics ; Medical sciences ; Middle Aged ; Molecular and cellular biology ; Oligonucleotides, Antisense - genetics ; Oligonucleotides, Antisense - pharmacology ; Promoter Regions, Genetic ; Proto-Oncogene Protein c-ets-1 ; Proto-Oncogene Proteins - biosynthesis ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins c-ets ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - biosynthesis ; RNA, Messenger - genetics ; Transcription Factors - biosynthesis ; Transcription Factors - genetics ; Transduction, Genetic ; Tumors</subject><ispartof>Cancer research (Chicago, Ill.), 2000-11, Vol.60 (22), p.6519-6525</ispartof><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=834761$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11103822$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>OZAKI, Iwata</creatorcontrib><creatorcontrib>MIZUTA, Toshihiko</creatorcontrib><creatorcontrib>GANG ZHAO</creatorcontrib><creatorcontrib>YOTSUMOTO, Hiroaki</creatorcontrib><creatorcontrib>HARA, Toshiya</creatorcontrib><creatorcontrib>KAJIHARA, Susumu</creatorcontrib><creatorcontrib>HISATOMI, Akitaka</creatorcontrib><creatorcontrib>SAKAI, Takahiro</creatorcontrib><creatorcontrib>YAMAMOTO, Kyosuke</creatorcontrib><title>Involvement of the Ets-1 gene in overexpression of matrilysin in human hepatocellular carcinoma</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>Although matrix metalloproteinases (MMPs) are thought to be involved in the invasion and metastasis of a variety of malignant tumors, including human hepatocellular carcinoma (HCC), the mechanisms for the expression of MMPs in HCC are not known. To understand the mechanism(s) of MMP expression, the expression of matrilysin (MMP-7) and several genes of the Ets transcription factor family was investigated in human HCC and hepatoma-derived cell lines. The role of Ets-1 gene expression in HCC was also studied. Analysis by semiquantitative reverse transcription-PCR revealed that MMP-7 and Ets-1 are overexpressed and closely associated in HCC. To clarify the role of Ets-1, hepatoma cells were transduced with human Ets-1 or targeted with the Ets-1-specific antisense oligonucleotides. Cells stably transduced with the Ets-1 gene showed increased MMP-7 expression compared to parental and mock-transfected cells. Cells targeted with Ets-1-specific antisense oligonucleotides showed reduced expression of MMP-7. Cotransfection of cells with a MMP-7 promoter-reporter gene plasmid and an Ets-1 expression vector yielded an increase in MMP-7 promoter activity in an Ets-1-responsive element-dependent manner. Taken together, these data suggested that the Ets-1 oncogene is up-regulated and involved in the overexpression of MMP-7 in human HCC and may contribute to the progression of HCC.</description><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Hepatocellular - enzymology</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Cell physiology</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Down-Regulation</subject><subject>Ets-1 gene</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Liver Neoplasms - enzymology</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Matrix Metalloproteinase 7 - biosynthesis</subject><subject>Matrix Metalloproteinase 7 - genetics</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Molecular and cellular biology</subject><subject>Oligonucleotides, Antisense - genetics</subject><subject>Oligonucleotides, Antisense - pharmacology</subject><subject>Promoter Regions, Genetic</subject><subject>Proto-Oncogene Protein c-ets-1</subject><subject>Proto-Oncogene Proteins - biosynthesis</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Proto-Oncogene Proteins c-ets</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - biosynthesis</subject><subject>RNA, Messenger - genetics</subject><subject>Transcription Factors - biosynthesis</subject><subject>Transcription Factors - genetics</subject><subject>Transduction, Genetic</subject><subject>Tumors</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE9Lw0AQxRdRbK1-BQkI3gL7t5scpVQtFLzoOUySiV1JduPupthv7xarV2F4w2N-DG_mjMyZEkWupVTnZE4pLXIlNZ-RqxA-klWMqksyY4xRUXA-J9XG7l2_xwFtzFyXxR1m6xhylr2jxczYzO3R49foMQTj7JEZIHrTH0IaptpNAyTFEaJrsO-nHnzWgG-MdQNck4sO-oA3p74gb4_r19Vzvn152qwetvlOUBrzgjKhRAmqrllDBdZUdsA6LFLITnQStaKq5qVQDEu21ELULeNctajSSViKBbn_2Tt69zlhiNVgwjEOWHRTqDSXYlkm-Q9kuqRSS53A2xM41QO21ejNAP5Q_f4uAXcnAEIDfefBNib8cYWQesnEN0ITd98</recordid><startdate>20001115</startdate><enddate>20001115</enddate><creator>OZAKI, Iwata</creator><creator>MIZUTA, Toshihiko</creator><creator>GANG ZHAO</creator><creator>YOTSUMOTO, Hiroaki</creator><creator>HARA, Toshiya</creator><creator>KAJIHARA, Susumu</creator><creator>HISATOMI, Akitaka</creator><creator>SAKAI, Takahiro</creator><creator>YAMAMOTO, Kyosuke</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7TO</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20001115</creationdate><title>Involvement of the Ets-1 gene in overexpression of matrilysin in human hepatocellular carcinoma</title><author>OZAKI, Iwata ; MIZUTA, Toshihiko ; GANG ZHAO ; YOTSUMOTO, Hiroaki ; HARA, Toshiya ; KAJIHARA, Susumu ; HISATOMI, Akitaka ; SAKAI, Takahiro ; YAMAMOTO, Kyosuke</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h300t-8013539a5bb1c03eb04fa1fe8822f3f4e7505b29351e916733bd1225de5510e93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Hepatocellular - enzymology</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Cell physiology</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Down-Regulation</topic><topic>Ets-1 gene</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Liver Neoplasms - enzymology</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Matrix Metalloproteinase 7 - biosynthesis</topic><topic>Matrix Metalloproteinase 7 - genetics</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Molecular and cellular biology</topic><topic>Oligonucleotides, Antisense - genetics</topic><topic>Oligonucleotides, Antisense - pharmacology</topic><topic>Promoter Regions, Genetic</topic><topic>Proto-Oncogene Protein c-ets-1</topic><topic>Proto-Oncogene Proteins - biosynthesis</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Proto-Oncogene Proteins c-ets</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - biosynthesis</topic><topic>RNA, Messenger - genetics</topic><topic>Transcription Factors - biosynthesis</topic><topic>Transcription Factors - genetics</topic><topic>Transduction, Genetic</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>OZAKI, Iwata</creatorcontrib><creatorcontrib>MIZUTA, Toshihiko</creatorcontrib><creatorcontrib>GANG ZHAO</creatorcontrib><creatorcontrib>YOTSUMOTO, Hiroaki</creatorcontrib><creatorcontrib>HARA, Toshiya</creatorcontrib><creatorcontrib>KAJIHARA, Susumu</creatorcontrib><creatorcontrib>HISATOMI, Akitaka</creatorcontrib><creatorcontrib>SAKAI, Takahiro</creatorcontrib><creatorcontrib>YAMAMOTO, Kyosuke</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>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>OZAKI, Iwata</au><au>MIZUTA, Toshihiko</au><au>GANG ZHAO</au><au>YOTSUMOTO, Hiroaki</au><au>HARA, Toshiya</au><au>KAJIHARA, Susumu</au><au>HISATOMI, Akitaka</au><au>SAKAI, Takahiro</au><au>YAMAMOTO, Kyosuke</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Involvement of the Ets-1 gene in overexpression of matrilysin in human hepatocellular carcinoma</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2000-11-15</date><risdate>2000</risdate><volume>60</volume><issue>22</issue><spage>6519</spage><epage>6525</epage><pages>6519-6525</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><abstract>Although matrix metalloproteinases (MMPs) are thought to be involved in the invasion and metastasis of a variety of malignant tumors, including human hepatocellular carcinoma (HCC), the mechanisms for the expression of MMPs in HCC are not known. To understand the mechanism(s) of MMP expression, the expression of matrilysin (MMP-7) and several genes of the Ets transcription factor family was investigated in human HCC and hepatoma-derived cell lines. The role of Ets-1 gene expression in HCC was also studied. Analysis by semiquantitative reverse transcription-PCR revealed that MMP-7 and Ets-1 are overexpressed and closely associated in HCC. To clarify the role of Ets-1, hepatoma cells were transduced with human Ets-1 or targeted with the Ets-1-specific antisense oligonucleotides. Cells stably transduced with the Ets-1 gene showed increased MMP-7 expression compared to parental and mock-transfected cells. Cells targeted with Ets-1-specific antisense oligonucleotides showed reduced expression of MMP-7. Cotransfection of cells with a MMP-7 promoter-reporter gene plasmid and an Ets-1 expression vector yielded an increase in MMP-7 promoter activity in an Ets-1-responsive element-dependent manner. Taken together, these data suggested that the Ets-1 oncogene is up-regulated and involved in the overexpression of MMP-7 in human HCC and may contribute to the progression of HCC.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>11103822</pmid><tpages>7</tpages></addata></record> |
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| subjects | Aged Biological and medical sciences Carcinoma, Hepatocellular - enzymology Carcinoma, Hepatocellular - genetics Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Down-Regulation Ets-1 gene Female Fundamental and applied biological sciences. Psychology Gastroenterology. Liver. Pancreas. Abdomen Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Humans Liver Neoplasms - enzymology Liver Neoplasms - genetics Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Matrix Metalloproteinase 7 - biosynthesis Matrix Metalloproteinase 7 - genetics Medical sciences Middle Aged Molecular and cellular biology Oligonucleotides, Antisense - genetics Oligonucleotides, Antisense - pharmacology Promoter Regions, Genetic Proto-Oncogene Protein c-ets-1 Proto-Oncogene Proteins - biosynthesis Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins c-ets Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - biosynthesis RNA, Messenger - genetics Transcription Factors - biosynthesis Transcription Factors - genetics Transduction, Genetic Tumors |
| title | Involvement of the Ets-1 gene in overexpression of matrilysin in human hepatocellular carcinoma |
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