Induction of a β-catenin-LEF-1 complex by wnt-1 and transforming mutants of β-catenin
Signal transduction by beta-catenin involves its posttranslational stabilization and import to the nucleus where it interacts with transcription factors. Recent implications for beta-catenin signaling in cancer prompted us to examine colon cancer cell lines for the expression of LEF-1, a transcripti...
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| Veröffentlicht in: | Oncogene 1997-12, Vol.15 (23), p.2833-2839 |
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| creator | PORFIRI, E RUBINFELD, B ALBERT, I HOVANES, K WATERMAN, M POLAKIS, P |
| description | Signal transduction by beta-catenin involves its posttranslational stabilization and import to the nucleus where it interacts with transcription factors. Recent implications for beta-catenin signaling in cancer prompted us to examine colon cancer cell lines for the expression of LEF-1, a transcription factor that binds to beta-catenin. The analysis of several cell lines revealed the expression of LEF1 mRNA and a constitutive association of the LEF-1 protein with beta-catenin. In contrast to the colon cells, PC12 and 293 cells did not contain a beta-catenin-LEF-1 complex, even though both proteins were detected in cell lysates. In these cells, the association of endogenous LEF1 and beta-catenin was induced by stimulation with the wnt-1 proto-oncogene. The complex formed following transient stimulation with wnt-1 and also persisted in cells stably expressing wnt-1. Ectopic overexpression of beta-catenin in 293 cells also induced the assembly of the beta-catenin-LEF-1 complex and activated gene transcription from a LEF-1-dependent promotor. Expression of mutant oncogenic forms of beta-catenin identified in cancer cells resulted in higher levels of transcriptional activity. The results suggest that a cancer pathway driven by wnt-1, or mutant forms of beta-catenin, may involve the formation of a persistent transcriptionally active complex of beta-catenin and LEF1. |
| doi_str_mv | 10.1038/sj.onc.1201462 |
| format | Article |
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Recent implications for beta-catenin signaling in cancer prompted us to examine colon cancer cell lines for the expression of LEF-1, a transcription factor that binds to beta-catenin. The analysis of several cell lines revealed the expression of LEF1 mRNA and a constitutive association of the LEF-1 protein with beta-catenin. In contrast to the colon cells, PC12 and 293 cells did not contain a beta-catenin-LEF-1 complex, even though both proteins were detected in cell lysates. In these cells, the association of endogenous LEF1 and beta-catenin was induced by stimulation with the wnt-1 proto-oncogene. The complex formed following transient stimulation with wnt-1 and also persisted in cells stably expressing wnt-1. Ectopic overexpression of beta-catenin in 293 cells also induced the assembly of the beta-catenin-LEF-1 complex and activated gene transcription from a LEF-1-dependent promotor. Expression of mutant oncogenic forms of beta-catenin identified in cancer cells resulted in higher levels of transcriptional activity. The results suggest that a cancer pathway driven by wnt-1, or mutant forms of beta-catenin, may involve the formation of a persistent transcriptionally active complex of beta-catenin and LEF1.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/sj.onc.1201462</identifier><identifier>PMID: 9419974</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing</publisher><subject>Animals ; beta Catenin ; Biological and medical sciences ; Cadherins - genetics ; Cadherins - physiology ; Cancer ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Cell Transformation, Neoplastic - genetics ; Cell Transformation, Neoplastic - metabolism ; Colon cancer ; Colonic Neoplasms ; Colorectal cancer ; Cytoskeletal Proteins - analysis ; Cytoskeletal Proteins - biosynthesis ; Cytoskeletal Proteins - genetics ; DNA-Binding Proteins - analysis ; DNA-Binding Proteins - biosynthesis ; DNA-Binding Proteins - genetics ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Humans ; Immunoblotting ; LEF protein ; LEF-1 protein ; Lymphoid Enhancer-Binding Factor 1 ; Lysates ; Melanoma ; Mice ; Molecular and cellular biology ; Mutants ; Mutation ; PC12 Cells ; Post-translation ; Precipitin Tests ; Proto-Oncogene Proteins - physiology ; Rats ; Signal transduction ; Signal Transduction - genetics ; Trans-Activators ; Transcription factors ; Transcription Factors - analysis ; Transcription Factors - biosynthesis ; Transcription Factors - genetics ; Tumor cell lines ; Tumor Cells, Cultured ; Wnt protein ; Wnt Proteins ; Wnt1 Protein ; Zebrafish Proteins ; β-Catenin</subject><ispartof>Oncogene, 1997-12, Vol.15 (23), p.2833-2839</ispartof><rights>1998 INIST-CNRS</rights><rights>Macmillan Publishers Limited 1997.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c418t-a8369ab288e5ef22f59059e9e4f19fe0462ec8ccf0f016d60b1706d0064b12233</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2098435$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9419974$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>PORFIRI, E</creatorcontrib><creatorcontrib>RUBINFELD, B</creatorcontrib><creatorcontrib>ALBERT, I</creatorcontrib><creatorcontrib>HOVANES, K</creatorcontrib><creatorcontrib>WATERMAN, M</creatorcontrib><creatorcontrib>POLAKIS, P</creatorcontrib><title>Induction of a β-catenin-LEF-1 complex by wnt-1 and transforming mutants of β-catenin</title><title>Oncogene</title><addtitle>Oncogene</addtitle><description>Signal transduction by beta-catenin involves its posttranslational stabilization and import to the nucleus where it interacts with transcription factors. Recent implications for beta-catenin signaling in cancer prompted us to examine colon cancer cell lines for the expression of LEF-1, a transcription factor that binds to beta-catenin. The analysis of several cell lines revealed the expression of LEF1 mRNA and a constitutive association of the LEF-1 protein with beta-catenin. In contrast to the colon cells, PC12 and 293 cells did not contain a beta-catenin-LEF-1 complex, even though both proteins were detected in cell lysates. In these cells, the association of endogenous LEF1 and beta-catenin was induced by stimulation with the wnt-1 proto-oncogene. The complex formed following transient stimulation with wnt-1 and also persisted in cells stably expressing wnt-1. Ectopic overexpression of beta-catenin in 293 cells also induced the assembly of the beta-catenin-LEF-1 complex and activated gene transcription from a LEF-1-dependent promotor. Expression of mutant oncogenic forms of beta-catenin identified in cancer cells resulted in higher levels of transcriptional activity. The results suggest that a cancer pathway driven by wnt-1, or mutant forms of beta-catenin, may involve the formation of a persistent transcriptionally active complex of beta-catenin and LEF1.</description><subject>Animals</subject><subject>beta Catenin</subject><subject>Biological and medical sciences</subject><subject>Cadherins - genetics</subject><subject>Cadherins - physiology</subject><subject>Cancer</subject><subject>Cell physiology</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>Cell Transformation, Neoplastic - metabolism</subject><subject>Colon cancer</subject><subject>Colonic Neoplasms</subject><subject>Colorectal cancer</subject><subject>Cytoskeletal Proteins - analysis</subject><subject>Cytoskeletal Proteins - biosynthesis</subject><subject>Cytoskeletal Proteins - genetics</subject><subject>DNA-Binding Proteins - analysis</subject><subject>DNA-Binding Proteins - biosynthesis</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>LEF protein</subject><subject>LEF-1 protein</subject><subject>Lymphoid Enhancer-Binding Factor 1</subject><subject>Lysates</subject><subject>Melanoma</subject><subject>Mice</subject><subject>Molecular and cellular biology</subject><subject>Mutants</subject><subject>Mutation</subject><subject>PC12 Cells</subject><subject>Post-translation</subject><subject>Precipitin Tests</subject><subject>Proto-Oncogene Proteins - physiology</subject><subject>Rats</subject><subject>Signal transduction</subject><subject>Signal Transduction - genetics</subject><subject>Trans-Activators</subject><subject>Transcription factors</subject><subject>Transcription Factors - analysis</subject><subject>Transcription Factors - biosynthesis</subject><subject>Transcription Factors - genetics</subject><subject>Tumor cell lines</subject><subject>Tumor Cells, Cultured</subject><subject>Wnt protein</subject><subject>Wnt Proteins</subject><subject>Wnt1 Protein</subject><subject>Zebrafish Proteins</subject><subject>β-Catenin</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFr3DAQhUVoSLebXHsrGBpy83ZGkmXpWJYkXVjIJaFHIctS8GJLW8um3b_VH9LfFC8xW8glp4GZ7z148wj5jLBCYPJb2q1isCukgFzQM7JAXoq8KBT_QBagCsgVZfQj-ZTSDgBKBfSCXCiOSpV8QX5uQj3aoYkhiz4z2b-_uTWDC03It7d3OWY2dvvW_cmqQ_Y7DNPChDobehOSj33XhOesGwcThnTU_1dfknNv2uSu5rkkT3e3j-sf-fbhfrP-vs0tRznkRjKhTEWldIXzlPpCQaGcctyj8g6mSM5Kaz14QFELqLAEUQMIXiGljC3Jzavvvo-_RpcG3TXJurY1wcUx6VJxRVHSd0EUDBTnR8evb8BdHPswhdBUcKQM5cQuyeqVsn1MqXde7_umM_1BI-hjMTrt9FSMnouZBF9m27HqXH3C5yam-_V8N8ma1k8ftk06YRSU5KxgL73QlX4</recordid><startdate>19971204</startdate><enddate>19971204</enddate><creator>PORFIRI, E</creator><creator>RUBINFELD, B</creator><creator>ALBERT, I</creator><creator>HOVANES, K</creator><creator>WATERMAN, M</creator><creator>POLAKIS, P</creator><general>Nature Publishing</general><general>Nature Publishing Group</general><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>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>19971204</creationdate><title>Induction of a β-catenin-LEF-1 complex by wnt-1 and transforming mutants of β-catenin</title><author>PORFIRI, E ; RUBINFELD, B ; ALBERT, I ; HOVANES, K ; WATERMAN, M ; POLAKIS, P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c418t-a8369ab288e5ef22f59059e9e4f19fe0462ec8ccf0f016d60b1706d0064b12233</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Animals</topic><topic>beta Catenin</topic><topic>Biological and medical sciences</topic><topic>Cadherins - genetics</topic><topic>Cadherins - physiology</topic><topic>Cancer</topic><topic>Cell physiology</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Cell Transformation, Neoplastic - genetics</topic><topic>Cell Transformation, Neoplastic - metabolism</topic><topic>Colon cancer</topic><topic>Colonic Neoplasms</topic><topic>Colorectal cancer</topic><topic>Cytoskeletal Proteins - analysis</topic><topic>Cytoskeletal Proteins - biosynthesis</topic><topic>Cytoskeletal Proteins - genetics</topic><topic>DNA-Binding Proteins - analysis</topic><topic>DNA-Binding Proteins - biosynthesis</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene expression</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>LEF protein</topic><topic>LEF-1 protein</topic><topic>Lymphoid Enhancer-Binding Factor 1</topic><topic>Lysates</topic><topic>Melanoma</topic><topic>Mice</topic><topic>Molecular and cellular biology</topic><topic>Mutants</topic><topic>Mutation</topic><topic>PC12 Cells</topic><topic>Post-translation</topic><topic>Precipitin Tests</topic><topic>Proto-Oncogene Proteins - physiology</topic><topic>Rats</topic><topic>Signal transduction</topic><topic>Signal Transduction - genetics</topic><topic>Trans-Activators</topic><topic>Transcription factors</topic><topic>Transcription Factors - analysis</topic><topic>Transcription Factors - biosynthesis</topic><topic>Transcription Factors - genetics</topic><topic>Tumor cell lines</topic><topic>Tumor Cells, Cultured</topic><topic>Wnt protein</topic><topic>Wnt Proteins</topic><topic>Wnt1 Protein</topic><topic>Zebrafish Proteins</topic><topic>β-Catenin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>PORFIRI, E</creatorcontrib><creatorcontrib>RUBINFELD, B</creatorcontrib><creatorcontrib>ALBERT, I</creatorcontrib><creatorcontrib>HOVANES, K</creatorcontrib><creatorcontrib>WATERMAN, M</creatorcontrib><creatorcontrib>POLAKIS, P</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>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>PORFIRI, E</au><au>RUBINFELD, B</au><au>ALBERT, I</au><au>HOVANES, K</au><au>WATERMAN, M</au><au>POLAKIS, P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Induction of a β-catenin-LEF-1 complex by wnt-1 and transforming mutants of β-catenin</atitle><jtitle>Oncogene</jtitle><addtitle>Oncogene</addtitle><date>1997-12-04</date><risdate>1997</risdate><volume>15</volume><issue>23</issue><spage>2833</spage><epage>2839</epage><pages>2833-2839</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><abstract>Signal transduction by beta-catenin involves its posttranslational stabilization and import to the nucleus where it interacts with transcription factors. Recent implications for beta-catenin signaling in cancer prompted us to examine colon cancer cell lines for the expression of LEF-1, a transcription factor that binds to beta-catenin. The analysis of several cell lines revealed the expression of LEF1 mRNA and a constitutive association of the LEF-1 protein with beta-catenin. In contrast to the colon cells, PC12 and 293 cells did not contain a beta-catenin-LEF-1 complex, even though both proteins were detected in cell lysates. In these cells, the association of endogenous LEF1 and beta-catenin was induced by stimulation with the wnt-1 proto-oncogene. The complex formed following transient stimulation with wnt-1 and also persisted in cells stably expressing wnt-1. Ectopic overexpression of beta-catenin in 293 cells also induced the assembly of the beta-catenin-LEF-1 complex and activated gene transcription from a LEF-1-dependent promotor. Expression of mutant oncogenic forms of beta-catenin identified in cancer cells resulted in higher levels of transcriptional activity. The results suggest that a cancer pathway driven by wnt-1, or mutant forms of beta-catenin, may involve the formation of a persistent transcriptionally active complex of beta-catenin and LEF1.</abstract><cop>Basingstoke</cop><pub>Nature Publishing</pub><pmid>9419974</pmid><doi>10.1038/sj.onc.1201462</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Nature; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SpringerLink Journals - AutoHoldings |
| subjects | Animals beta Catenin Biological and medical sciences Cadherins - genetics Cadherins - physiology Cancer Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cell Transformation, Neoplastic - genetics Cell Transformation, Neoplastic - metabolism Colon cancer Colonic Neoplasms Colorectal cancer Cytoskeletal Proteins - analysis Cytoskeletal Proteins - biosynthesis Cytoskeletal Proteins - genetics DNA-Binding Proteins - analysis DNA-Binding Proteins - biosynthesis DNA-Binding Proteins - genetics Fundamental and applied biological sciences. Psychology Gene expression Humans Immunoblotting LEF protein LEF-1 protein Lymphoid Enhancer-Binding Factor 1 Lysates Melanoma Mice Molecular and cellular biology Mutants Mutation PC12 Cells Post-translation Precipitin Tests Proto-Oncogene Proteins - physiology Rats Signal transduction Signal Transduction - genetics Trans-Activators Transcription factors Transcription Factors - analysis Transcription Factors - biosynthesis Transcription Factors - genetics Tumor cell lines Tumor Cells, Cultured Wnt protein Wnt Proteins Wnt1 Protein Zebrafish Proteins β-Catenin |
| title | Induction of a β-catenin-LEF-1 complex by wnt-1 and transforming mutants of β-catenin |
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