Expression of Dominant Negative Form of PAX4 in Human Insulinoma
The paired-homeodomain transcription factor PAX4 is expressed in the early pancreas, but is later restricted to β cells and not expressed in mature islets, suggesting an important role of PAX4 in differentiation and development of pancreatic islet. Here we show that PAX4 mRNA was highly expressed in...
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Veröffentlicht in: | Biochemical and biophysical research communications 2001-03, Vol.282 (1), p.34-40 |
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creator | Miyamoto, Takahide Kakizawa, Tomoko Ichikawa, Kazuo Nishio, Shinichi Kajikawa, Shoji Hashizume, Kiyoshi |
description | The paired-homeodomain transcription factor PAX4 is expressed in the early pancreas, but is later restricted to β cells and not expressed in mature islets, suggesting an important role of PAX4 in differentiation and development of pancreatic islet. Here we show that PAX4 mRNA was highly expressed in human insulinoma tissues, whereas little if any mRNA was expressed in normal islets. Furthermore, this insulinoma associated expression of PAX4 mRNA was accompanied with expression of its novel variant form (PAX4v). PAX4v was generated by alternative splicing lacking the exon 7, and containing intact paired and homeo domain followed by novel 35 amino acids. PAX4v reversed the wild-type PAX4 mediated repression of the insulin promoter in cotransfection assays. PAX4v may play a role to antagonize the wild-type PAX4 function in human insulinoma. These data imply a role of PAX4 and PAX4v expression in tumorigenesis and development of insulinoma. |
doi_str_mv | 10.1006/bbrc.2001.4552 |
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Here we show that PAX4 mRNA was highly expressed in human insulinoma tissues, whereas little if any mRNA was expressed in normal islets. Furthermore, this insulinoma associated expression of PAX4 mRNA was accompanied with expression of its novel variant form (PAX4v). PAX4v was generated by alternative splicing lacking the exon 7, and containing intact paired and homeo domain followed by novel 35 amino acids. PAX4v reversed the wild-type PAX4 mediated repression of the insulin promoter in cotransfection assays. PAX4v may play a role to antagonize the wild-type PAX4 function in human insulinoma. These data imply a role of PAX4 and PAX4v expression in tumorigenesis and development of insulinoma.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1006/bbrc.2001.4552</identifier><identifier>PMID: 11263967</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amino Acid Sequence ; Animals ; Base Sequence ; Cricetinae ; Gene Expression Regulation ; Genes, Dominant ; Homeodomain Proteins - chemistry ; Homeodomain Proteins - genetics ; Humans ; insulin promoter ; insulinoma ; Insulinoma - genetics ; Insulinoma - pathology ; Molecular Sequence Data ; Paired Box Transcription Factors ; pancreatic β-cell ; PAX4 ; PAX4 variant ; RNA Splicing ; RNA, Messenger - genetics ; transcription ; Transcription Factors - chemistry ; Transcription Factors - genetics ; Transcription, Genetic ; Tumor Cells, Cultured</subject><ispartof>Biochemical and biophysical research communications, 2001-03, Vol.282 (1), p.34-40</ispartof><rights>2001 Academic Press</rights><rights>Copyright 2001 Academic Press.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c406t-24ee07671d73a833fcc40d9bbdfc8a9f279f4b5ad42c44b8c5d9de656a2bd39e3</citedby><cites>FETCH-LOGICAL-c406t-24ee07671d73a833fcc40d9bbdfc8a9f279f4b5ad42c44b8c5d9de656a2bd39e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/bbrc.2001.4552$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11263967$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Miyamoto, Takahide</creatorcontrib><creatorcontrib>Kakizawa, Tomoko</creatorcontrib><creatorcontrib>Ichikawa, Kazuo</creatorcontrib><creatorcontrib>Nishio, Shinichi</creatorcontrib><creatorcontrib>Kajikawa, Shoji</creatorcontrib><creatorcontrib>Hashizume, Kiyoshi</creatorcontrib><title>Expression of Dominant Negative Form of PAX4 in Human Insulinoma</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>The paired-homeodomain transcription factor PAX4 is expressed in the early pancreas, but is later restricted to β cells and not expressed in mature islets, suggesting an important role of PAX4 in differentiation and development of pancreatic islet. Here we show that PAX4 mRNA was highly expressed in human insulinoma tissues, whereas little if any mRNA was expressed in normal islets. Furthermore, this insulinoma associated expression of PAX4 mRNA was accompanied with expression of its novel variant form (PAX4v). PAX4v was generated by alternative splicing lacking the exon 7, and containing intact paired and homeo domain followed by novel 35 amino acids. PAX4v reversed the wild-type PAX4 mediated repression of the insulin promoter in cotransfection assays. PAX4v may play a role to antagonize the wild-type PAX4 function in human insulinoma. These data imply a role of PAX4 and PAX4v expression in tumorigenesis and development of insulinoma.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>Cricetinae</subject><subject>Gene Expression Regulation</subject><subject>Genes, Dominant</subject><subject>Homeodomain Proteins - chemistry</subject><subject>Homeodomain Proteins - genetics</subject><subject>Humans</subject><subject>insulin promoter</subject><subject>insulinoma</subject><subject>Insulinoma - genetics</subject><subject>Insulinoma - pathology</subject><subject>Molecular Sequence Data</subject><subject>Paired Box Transcription Factors</subject><subject>pancreatic β-cell</subject><subject>PAX4</subject><subject>PAX4 variant</subject><subject>RNA Splicing</subject><subject>RNA, Messenger - genetics</subject><subject>transcription</subject><subject>Transcription Factors - chemistry</subject><subject>Transcription Factors - genetics</subject><subject>Transcription, Genetic</subject><subject>Tumor Cells, Cultured</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kEFLwzAUgIMobk6vHqUnb51JmqbNzaGbGwz1oLBbSJNXiazJTNqh_96WDTx5Crx874P3IXRN8JRgzO-qKugpxZhMWZ7TEzQmWOCUEsxO0Rj3REoF2YzQRYyfPUUYF-doRAjlmeDFGN3Pv3cBYrTeJb5OHn1jnXJt8gwfqrV7SBY-NMPP62zDEuuSZdcol6xc7LbW-UZdorNabSNcHd8Jel_M3x6W6frlafUwW6eaYd6mlAHgghfEFJkqs6zW_dyIqjK1LpWoaSFqVuXKMKoZq0qdG2GA51zRymQCsgm6PXh3wX91EFvZ2Khhu1UOfBdlwYUoenEPTg-gDj7GALXcBduo8CMJlkMzOTSTQzM5NOsXbo7mrmrA_OHHSD1QHgDo79tbCDJqC06DsQF0K423_7l_AQVVenY</recordid><startdate>20010323</startdate><enddate>20010323</enddate><creator>Miyamoto, Takahide</creator><creator>Kakizawa, Tomoko</creator><creator>Ichikawa, Kazuo</creator><creator>Nishio, Shinichi</creator><creator>Kajikawa, Shoji</creator><creator>Hashizume, Kiyoshi</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></search><sort><creationdate>20010323</creationdate><title>Expression of Dominant Negative Form of PAX4 in Human Insulinoma</title><author>Miyamoto, Takahide ; Kakizawa, Tomoko ; Ichikawa, Kazuo ; Nishio, Shinichi ; Kajikawa, Shoji ; Hashizume, Kiyoshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c406t-24ee07671d73a833fcc40d9bbdfc8a9f279f4b5ad42c44b8c5d9de656a2bd39e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>Cricetinae</topic><topic>Gene Expression Regulation</topic><topic>Genes, Dominant</topic><topic>Homeodomain Proteins - chemistry</topic><topic>Homeodomain Proteins - genetics</topic><topic>Humans</topic><topic>insulin promoter</topic><topic>insulinoma</topic><topic>Insulinoma - genetics</topic><topic>Insulinoma - pathology</topic><topic>Molecular Sequence Data</topic><topic>Paired Box Transcription Factors</topic><topic>pancreatic β-cell</topic><topic>PAX4</topic><topic>PAX4 variant</topic><topic>RNA Splicing</topic><topic>RNA, Messenger - genetics</topic><topic>transcription</topic><topic>Transcription Factors - chemistry</topic><topic>Transcription Factors - genetics</topic><topic>Transcription, Genetic</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miyamoto, Takahide</creatorcontrib><creatorcontrib>Kakizawa, Tomoko</creatorcontrib><creatorcontrib>Ichikawa, Kazuo</creatorcontrib><creatorcontrib>Nishio, Shinichi</creatorcontrib><creatorcontrib>Kajikawa, Shoji</creatorcontrib><creatorcontrib>Hashizume, Kiyoshi</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><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miyamoto, Takahide</au><au>Kakizawa, Tomoko</au><au>Ichikawa, Kazuo</au><au>Nishio, Shinichi</au><au>Kajikawa, Shoji</au><au>Hashizume, Kiyoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of Dominant Negative Form of PAX4 in Human Insulinoma</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2001-03-23</date><risdate>2001</risdate><volume>282</volume><issue>1</issue><spage>34</spage><epage>40</epage><pages>34-40</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>The paired-homeodomain transcription factor PAX4 is expressed in the early pancreas, but is later restricted to β cells and not expressed in mature islets, suggesting an important role of PAX4 in differentiation and development of pancreatic islet. Here we show that PAX4 mRNA was highly expressed in human insulinoma tissues, whereas little if any mRNA was expressed in normal islets. Furthermore, this insulinoma associated expression of PAX4 mRNA was accompanied with expression of its novel variant form (PAX4v). PAX4v was generated by alternative splicing lacking the exon 7, and containing intact paired and homeo domain followed by novel 35 amino acids. PAX4v reversed the wild-type PAX4 mediated repression of the insulin promoter in cotransfection assays. PAX4v may play a role to antagonize the wild-type PAX4 function in human insulinoma. These data imply a role of PAX4 and PAX4v expression in tumorigenesis and development of insulinoma.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>11263967</pmid><doi>10.1006/bbrc.2001.4552</doi><tpages>7</tpages></addata></record> |
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subjects | Amino Acid Sequence Animals Base Sequence Cricetinae Gene Expression Regulation Genes, Dominant Homeodomain Proteins - chemistry Homeodomain Proteins - genetics Humans insulin promoter insulinoma Insulinoma - genetics Insulinoma - pathology Molecular Sequence Data Paired Box Transcription Factors pancreatic β-cell PAX4 PAX4 variant RNA Splicing RNA, Messenger - genetics transcription Transcription Factors - chemistry Transcription Factors - genetics Transcription, Genetic Tumor Cells, Cultured |
title | Expression of Dominant Negative Form of PAX4 in Human Insulinoma |
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