Transgenic expression in the liver of truncated Met blocks apoptosis and permits immortalization of hepatocytes
Hepatocyte growth factor induces proliferation, motility and differentiation of epithelial cells through the tyrosine kinase receptor encoded by the MET proto‐oncogene. The cytoplasmic portion of Met (referred to as cyto‐Met) is activated but only weakly transforming. In order to determine the effec...
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| Veröffentlicht in: | The EMBO journal 1997-02, Vol.16 (3), p.495-503 |
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| creator | Amicone, Laura Spagnoli, Francesca M. Späth, Gerald Giordano, Silvia Tommasini, Cristina Bernardini, Silvia De Luca, Veronica Rocca, Carlo Della Weiss, Mary C. Comoglio, Paolo M. Tripodi, Marco |
| description | Hepatocyte growth factor induces proliferation, motility and differentiation of epithelial cells through the tyrosine kinase receptor encoded by the
MET
proto‐oncogene. The cytoplasmic portion of Met (referred to as cyto‐Met) is activated but only weakly transforming. In order to determine the effect of activated Met on hepatocytes, we have targeted truncated Met expression to the liver by incorporating the cDNA into a vector carrying the entire human
a‐1‐antitrypsin
transcriptional unit. Transgenic expression in the liver of truncated human Met, containing the regulatory and the catalytic cytoplasmic domains, renders hepatocytes constitutively resistant to apoptosis and reproducibly permits immortalization. The emerging stable cell lines are not transformed and maintain a highly differentiated phenotype judged by the retention of epithelial cell polarity and the expression of hepatocyte‐enriched transcription factors as well as hepatic products. |
| doi_str_mv | 10.1093/emboj/16.3.495 |
| format | Article |
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MET
proto‐oncogene. The cytoplasmic portion of Met (referred to as cyto‐Met) is activated but only weakly transforming. In order to determine the effect of activated Met on hepatocytes, we have targeted truncated Met expression to the liver by incorporating the cDNA into a vector carrying the entire human
a‐1‐antitrypsin
transcriptional unit. Transgenic expression in the liver of truncated human Met, containing the regulatory and the catalytic cytoplasmic domains, renders hepatocytes constitutively resistant to apoptosis and reproducibly permits immortalization. The emerging stable cell lines are not transformed and maintain a highly differentiated phenotype judged by the retention of epithelial cell polarity and the expression of hepatocyte‐enriched transcription factors as well as hepatic products.</description><identifier>ISSN: 0261-4189</identifier><identifier>ISSN: 1460-2075</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.1093/emboj/16.3.495</identifier><identifier>PMID: 9034332</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>alpha 1-Antitrypsin - genetics ; Animals ; Antibodies, Monoclonal - immunology ; Antibodies, Monoclonal - metabolism ; Antibodies, Monoclonal - pharmacology ; Apoptosis - genetics ; Apoptosis - physiology ; apoptosis protection ; Blotting, Northern ; Blotting, Southern ; Blotting, Western ; Cell Differentiation - genetics ; cell polarity ; Cells, Cultured ; Gene Expression Regulation, Developmental - genetics ; Hepatocyte Growth Factor - metabolism ; Histocytochemistry ; Humans ; immortalized hepatocytes ; Immunohistochemistry ; Liver - metabolism ; Met ; Mice ; Mice, Transgenic ; Microscopy, Electron ; Proto-Oncogenes - genetics ; Receptor Protein-Tyrosine Kinases - genetics ; Transgenes - genetics</subject><ispartof>The EMBO journal, 1997-02, Vol.16 (3), p.495-503</ispartof><rights>European Molecular Biology Organization 1997</rights><rights>Copyright © 1997 European Molecular Biology Organization</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6306-9d59547fdb84874b6e4facd64834352e09c84fc40df13fde211760e5354db0923</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1169653/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1169653/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1416,1432,27922,27923,45572,45573,46407,46831,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9034332$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Amicone, Laura</creatorcontrib><creatorcontrib>Spagnoli, Francesca M.</creatorcontrib><creatorcontrib>Späth, Gerald</creatorcontrib><creatorcontrib>Giordano, Silvia</creatorcontrib><creatorcontrib>Tommasini, Cristina</creatorcontrib><creatorcontrib>Bernardini, Silvia</creatorcontrib><creatorcontrib>De Luca, Veronica</creatorcontrib><creatorcontrib>Rocca, Carlo Della</creatorcontrib><creatorcontrib>Weiss, Mary C.</creatorcontrib><creatorcontrib>Comoglio, Paolo M.</creatorcontrib><creatorcontrib>Tripodi, Marco</creatorcontrib><title>Transgenic expression in the liver of truncated Met blocks apoptosis and permits immortalization of hepatocytes</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><addtitle>EMBO J</addtitle><description>Hepatocyte growth factor induces proliferation, motility and differentiation of epithelial cells through the tyrosine kinase receptor encoded by the
MET
proto‐oncogene. The cytoplasmic portion of Met (referred to as cyto‐Met) is activated but only weakly transforming. In order to determine the effect of activated Met on hepatocytes, we have targeted truncated Met expression to the liver by incorporating the cDNA into a vector carrying the entire human
a‐1‐antitrypsin
transcriptional unit. Transgenic expression in the liver of truncated human Met, containing the regulatory and the catalytic cytoplasmic domains, renders hepatocytes constitutively resistant to apoptosis and reproducibly permits immortalization. The emerging stable cell lines are not transformed and maintain a highly differentiated phenotype judged by the retention of epithelial cell polarity and the expression of hepatocyte‐enriched transcription factors as well as hepatic products.</description><subject>alpha 1-Antitrypsin - genetics</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibodies, Monoclonal - metabolism</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Apoptosis - genetics</subject><subject>Apoptosis - physiology</subject><subject>apoptosis protection</subject><subject>Blotting, Northern</subject><subject>Blotting, Southern</subject><subject>Blotting, Western</subject><subject>Cell Differentiation - genetics</subject><subject>cell polarity</subject><subject>Cells, Cultured</subject><subject>Gene Expression Regulation, Developmental - genetics</subject><subject>Hepatocyte Growth Factor - metabolism</subject><subject>Histocytochemistry</subject><subject>Humans</subject><subject>immortalized hepatocytes</subject><subject>Immunohistochemistry</subject><subject>Liver - metabolism</subject><subject>Met</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Microscopy, Electron</subject><subject>Proto-Oncogenes - genetics</subject><subject>Receptor Protein-Tyrosine Kinases - genetics</subject><subject>Transgenes - genetics</subject><issn>0261-4189</issn><issn>1460-2075</issn><issn>1460-2075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9v0zAcxSMEGmNw5YaUE7e0dvwj8QUJptGBNrgUlZvlON-07hI72M5Y-evxaFXg1JMtvfc-ftbLstcYzTASZA5D47ZzzGdkRgV7kp1jylFRooo9zc5RyXFBcS2eZy9C2CKEWF3hs-xMIEIJKc8zt_TKhjVYo3N4GD2EYJzNjc3jBvLe3IPPXZdHP1mtIrT5LcS86Z2-C7ka3RhdMOlm23wEP5gYcjMMzkfVm18qPqJSegOjik7vIoSX2bNO9QFeHc6L7NvHq-XldXHzdfHp8v1NoTlBvBAtE4xWXdvUtK5ow4F2Srec1qk3KwEJXdNOU9R2mHQtlBhXHAEjjLYNEiW5yN7tuePUDNBqsNGrXo7eDMrvpFNG_q9Ys5Frdy8x5oIzkgBvDwDvfkwQohxM0ND3yoKbgqzqGuOSi5NGzOqaIoaTcbY3au9C8NAd22AkH7eUf7aUmEsi05Yp8ObfPxzth_GSXu31n6aH3QmavLr98LliAiHKU3K-T4YUsmvwcusmb9MgJ7tYFScPx8f-Eou9bkKEh6Os_J3kFamYXH1ZyCVercQ1Wcjv5DeTi9iZ</recordid><startdate>19970201</startdate><enddate>19970201</enddate><creator>Amicone, Laura</creator><creator>Spagnoli, Francesca M.</creator><creator>Späth, Gerald</creator><creator>Giordano, Silvia</creator><creator>Tommasini, Cristina</creator><creator>Bernardini, Silvia</creator><creator>De Luca, Veronica</creator><creator>Rocca, Carlo Della</creator><creator>Weiss, Mary C.</creator><creator>Comoglio, Paolo M.</creator><creator>Tripodi, Marco</creator><general>John Wiley & Sons, Ltd</general><general>Nature Publishing Group UK</general><scope>BSCLL</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>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19970201</creationdate><title>Transgenic expression in the liver of truncated Met blocks apoptosis and permits immortalization of hepatocytes</title><author>Amicone, Laura ; Spagnoli, Francesca M. ; Späth, Gerald ; Giordano, Silvia ; Tommasini, Cristina ; Bernardini, Silvia ; De Luca, Veronica ; Rocca, Carlo Della ; Weiss, Mary C. ; Comoglio, Paolo M. ; Tripodi, Marco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6306-9d59547fdb84874b6e4facd64834352e09c84fc40df13fde211760e5354db0923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>alpha 1-Antitrypsin - genetics</topic><topic>Animals</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Antibodies, Monoclonal - metabolism</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Apoptosis - genetics</topic><topic>Apoptosis - physiology</topic><topic>apoptosis protection</topic><topic>Blotting, Northern</topic><topic>Blotting, Southern</topic><topic>Blotting, Western</topic><topic>Cell Differentiation - genetics</topic><topic>cell polarity</topic><topic>Cells, Cultured</topic><topic>Gene Expression Regulation, Developmental - genetics</topic><topic>Hepatocyte Growth Factor - metabolism</topic><topic>Histocytochemistry</topic><topic>Humans</topic><topic>immortalized hepatocytes</topic><topic>Immunohistochemistry</topic><topic>Liver - metabolism</topic><topic>Met</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Microscopy, Electron</topic><topic>Proto-Oncogenes - genetics</topic><topic>Receptor Protein-Tyrosine Kinases - genetics</topic><topic>Transgenes - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Amicone, Laura</creatorcontrib><creatorcontrib>Spagnoli, Francesca M.</creatorcontrib><creatorcontrib>Späth, Gerald</creatorcontrib><creatorcontrib>Giordano, Silvia</creatorcontrib><creatorcontrib>Tommasini, Cristina</creatorcontrib><creatorcontrib>Bernardini, Silvia</creatorcontrib><creatorcontrib>De Luca, Veronica</creatorcontrib><creatorcontrib>Rocca, Carlo Della</creatorcontrib><creatorcontrib>Weiss, Mary C.</creatorcontrib><creatorcontrib>Comoglio, Paolo M.</creatorcontrib><creatorcontrib>Tripodi, Marco</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The EMBO journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Amicone, Laura</au><au>Spagnoli, Francesca M.</au><au>Späth, Gerald</au><au>Giordano, Silvia</au><au>Tommasini, Cristina</au><au>Bernardini, Silvia</au><au>De Luca, Veronica</au><au>Rocca, Carlo Della</au><au>Weiss, Mary C.</au><au>Comoglio, Paolo M.</au><au>Tripodi, Marco</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transgenic expression in the liver of truncated Met blocks apoptosis and permits immortalization of hepatocytes</atitle><jtitle>The EMBO journal</jtitle><stitle>EMBO J</stitle><addtitle>EMBO J</addtitle><date>1997-02-01</date><risdate>1997</risdate><volume>16</volume><issue>3</issue><spage>495</spage><epage>503</epage><pages>495-503</pages><issn>0261-4189</issn><issn>1460-2075</issn><eissn>1460-2075</eissn><abstract>Hepatocyte growth factor induces proliferation, motility and differentiation of epithelial cells through the tyrosine kinase receptor encoded by the
MET
proto‐oncogene. The cytoplasmic portion of Met (referred to as cyto‐Met) is activated but only weakly transforming. In order to determine the effect of activated Met on hepatocytes, we have targeted truncated Met expression to the liver by incorporating the cDNA into a vector carrying the entire human
a‐1‐antitrypsin
transcriptional unit. Transgenic expression in the liver of truncated human Met, containing the regulatory and the catalytic cytoplasmic domains, renders hepatocytes constitutively resistant to apoptosis and reproducibly permits immortalization. The emerging stable cell lines are not transformed and maintain a highly differentiated phenotype judged by the retention of epithelial cell polarity and the expression of hepatocyte‐enriched transcription factors as well as hepatic products.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>9034332</pmid><doi>10.1093/emboj/16.3.495</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0261-4189 |
| ispartof | The EMBO journal, 1997-02, Vol.16 (3), p.495-503 |
| issn | 0261-4189 1460-2075 1460-2075 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1169653 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Wiley Free Content; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | alpha 1-Antitrypsin - genetics Animals Antibodies, Monoclonal - immunology Antibodies, Monoclonal - metabolism Antibodies, Monoclonal - pharmacology Apoptosis - genetics Apoptosis - physiology apoptosis protection Blotting, Northern Blotting, Southern Blotting, Western Cell Differentiation - genetics cell polarity Cells, Cultured Gene Expression Regulation, Developmental - genetics Hepatocyte Growth Factor - metabolism Histocytochemistry Humans immortalized hepatocytes Immunohistochemistry Liver - metabolism Met Mice Mice, Transgenic Microscopy, Electron Proto-Oncogenes - genetics Receptor Protein-Tyrosine Kinases - genetics Transgenes - genetics |
| title | Transgenic expression in the liver of truncated Met blocks apoptosis and permits immortalization of hepatocytes |
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