ITF-2, a downstream target of the Wnt/TCF pathway, is activated in human cancers with β-catenin defects and promotes neoplastic transformation
In many cancers, inactivation of the adenomatous polyposis coli (APC) or Axin tumor suppressor proteins or activating mutations in β-catenin lead to elevated β-catenin levels, enhanced binding of β-catenin to T cell factor (TCF) proteins, and increased expression of TCF-regulated genes. We found tha...
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| creator | Kolligs, Frank T. Nieman, Marvin T. Winer, Ira Hu, Gang Van Mater, David Feng, Ying Smith, Ian M. Wu, Rong Zhai, Yali Cho, Kathleen R. Fearon, Eric R. |
| description | In many cancers, inactivation of the adenomatous polyposis coli (APC) or Axin tumor suppressor proteins or activating mutations in β-catenin lead to elevated β-catenin levels, enhanced binding of β-catenin to T cell factor (TCF) proteins, and increased expression of TCF-regulated genes. We found that the gene for the basic helix-loop-helix transcription factor ITF-2 (immunoglobulin transcription factor-2) was activated in rat E1A-immortalized RK3E cells following neoplastic transformation by β-catenin or ligand-induced activation of a β-catenin-estrogen receptor fusion protein. Human cancers with β-catenin regulatory defects had elevated
ITF-2 expression, and
ITF-2 was repressed by restoring wild-type APC function or inhibiting TCF activity. Of note,
ITF-2 promoted neoplastic transformation of RK3E cells. We propose that
ITF-2 is a TCF-regulated gene, which functions in concert with other TCF target genes to promote growth and/or survival of cancer cells with defects in β-catenin regulation. |
| doi_str_mv | 10.1016/S1535-6108(02)00035-1 |
| format | Article |
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ITF-2 expression, and
ITF-2 was repressed by restoring wild-type APC function or inhibiting TCF activity. Of note,
ITF-2 promoted neoplastic transformation of RK3E cells. We propose that
ITF-2 is a TCF-regulated gene, which functions in concert with other TCF target genes to promote growth and/or survival of cancer cells with defects in β-catenin regulation.</description><identifier>ISSN: 1535-6108</identifier><identifier>EISSN: 1878-3686</identifier><identifier>DOI: 10.1016/S1535-6108(02)00035-1</identifier><identifier>PMID: 12086873</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; beta Catenin ; Cell Transformation, Neoplastic - genetics ; Cell Transformation, Neoplastic - metabolism ; Cytoskeletal Proteins - genetics ; Cytoskeletal Proteins - metabolism ; DNA-Binding Proteins - metabolism ; Female ; Humans ; Lymphoid Enhancer-Binding Factor 1 ; Mutation - genetics ; Neoplasms - metabolism ; Ovarian Neoplasms - metabolism ; Ovarian Neoplasms - pathology ; Proto-Oncogene Proteins - metabolism ; Rats ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Signal Transduction ; TCF Transcription Factors ; Trans-Activators - metabolism ; Transcription Factor 4 ; Transcription Factor 7-Like 2 Protein ; Transcription Factors - metabolism ; Tumor Cells, Cultured ; Wnt Proteins ; Zebrafish Proteins</subject><ispartof>Cancer cell, 2002-03, Vol.1 (2), p.145-155</ispartof><rights>2002 Cell Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c439t-3824aafac6a2e812d9571cf84ffb9741db406008ea8a0007ca6d6fa9342e34603</citedby><cites>FETCH-LOGICAL-c439t-3824aafac6a2e812d9571cf84ffb9741db406008ea8a0007ca6d6fa9342e34603</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S1535-6108(02)00035-1$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12086873$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kolligs, Frank T.</creatorcontrib><creatorcontrib>Nieman, Marvin T.</creatorcontrib><creatorcontrib>Winer, Ira</creatorcontrib><creatorcontrib>Hu, Gang</creatorcontrib><creatorcontrib>Van Mater, David</creatorcontrib><creatorcontrib>Feng, Ying</creatorcontrib><creatorcontrib>Smith, Ian M.</creatorcontrib><creatorcontrib>Wu, Rong</creatorcontrib><creatorcontrib>Zhai, Yali</creatorcontrib><creatorcontrib>Cho, Kathleen R.</creatorcontrib><creatorcontrib>Fearon, Eric R.</creatorcontrib><title>ITF-2, a downstream target of the Wnt/TCF pathway, is activated in human cancers with β-catenin defects and promotes neoplastic transformation</title><title>Cancer cell</title><addtitle>Cancer Cell</addtitle><description>In many cancers, inactivation of the adenomatous polyposis coli (APC) or Axin tumor suppressor proteins or activating mutations in β-catenin lead to elevated β-catenin levels, enhanced binding of β-catenin to T cell factor (TCF) proteins, and increased expression of TCF-regulated genes. We found that the gene for the basic helix-loop-helix transcription factor ITF-2 (immunoglobulin transcription factor-2) was activated in rat E1A-immortalized RK3E cells following neoplastic transformation by β-catenin or ligand-induced activation of a β-catenin-estrogen receptor fusion protein. Human cancers with β-catenin regulatory defects had elevated
ITF-2 expression, and
ITF-2 was repressed by restoring wild-type APC function or inhibiting TCF activity. Of note,
ITF-2 promoted neoplastic transformation of RK3E cells. We propose that
ITF-2 is a TCF-regulated gene, which functions in concert with other TCF target genes to promote growth and/or survival of cancer cells with defects in β-catenin regulation.</description><subject>Animals</subject><subject>beta Catenin</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>Cell Transformation, Neoplastic - metabolism</subject><subject>Cytoskeletal Proteins - genetics</subject><subject>Cytoskeletal Proteins - metabolism</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Female</subject><subject>Humans</subject><subject>Lymphoid Enhancer-Binding Factor 1</subject><subject>Mutation - genetics</subject><subject>Neoplasms - metabolism</subject><subject>Ovarian Neoplasms - metabolism</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Rats</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Signal Transduction</subject><subject>TCF Transcription Factors</subject><subject>Trans-Activators - metabolism</subject><subject>Transcription Factor 4</subject><subject>Transcription Factor 7-Like 2 Protein</subject><subject>Transcription Factors - metabolism</subject><subject>Tumor Cells, Cultured</subject><subject>Wnt Proteins</subject><subject>Zebrafish Proteins</subject><issn>1535-6108</issn><issn>1878-3686</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFuEzEQhi1ERUvhEUA-IZC61F57vd5ThSJCK1XiQBBHa2KPiVHWG2ynUZ-Cd-FBeCbcJlWPPXms-f6Z0f8T8oazj5xxdf6Nd6JrFGf6PWs_MMbqjz8jJ1z3uhFKq-e1fkCOycucf7Gq4_3wghzzlmmle3FC_lwt5k17RoG6aRdzSQgjLZB-YqGTp2WF9Ecs54vZnG6grHZwe0ZDpmBLuIGCjoZIV9sRIrUQLaZMd6Gs6L-_ja3tWLsOPdpSJdHRTZrGqWCmEafNGnIJlpYEMfspjVDCFF-RIw_rjK8P7yn5Pv-8mF0211-_XM0-XTdWiqE0QrcSwINV0KLmrRu6nluvpffLoZfcLSVTjGkEDdWb3oJyysMgZItCKiZOybv93HrS7y3mYsaQLa7XUE_bZtNz3Q1q6J4EuRZaSDlUsNuDNk05J_Rmk8II6dZwZu4iM_eRmbs8DGvNfWSGV93bw4LtckT3qDpkVIGLPYDVj5uAyWQbsJrtQqrOGjeFJ1b8B29Ip7w</recordid><startdate>20020301</startdate><enddate>20020301</enddate><creator>Kolligs, Frank T.</creator><creator>Nieman, Marvin T.</creator><creator>Winer, Ira</creator><creator>Hu, Gang</creator><creator>Van Mater, David</creator><creator>Feng, Ying</creator><creator>Smith, Ian M.</creator><creator>Wu, Rong</creator><creator>Zhai, Yali</creator><creator>Cho, Kathleen R.</creator><creator>Fearon, Eric R.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</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>H94</scope><scope>7X8</scope></search><sort><creationdate>20020301</creationdate><title>ITF-2, a downstream target of the Wnt/TCF pathway, is activated in human cancers with β-catenin defects and promotes neoplastic transformation</title><author>Kolligs, Frank T. ; 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We found that the gene for the basic helix-loop-helix transcription factor ITF-2 (immunoglobulin transcription factor-2) was activated in rat E1A-immortalized RK3E cells following neoplastic transformation by β-catenin or ligand-induced activation of a β-catenin-estrogen receptor fusion protein. Human cancers with β-catenin regulatory defects had elevated
ITF-2 expression, and
ITF-2 was repressed by restoring wild-type APC function or inhibiting TCF activity. Of note,
ITF-2 promoted neoplastic transformation of RK3E cells. We propose that
ITF-2 is a TCF-regulated gene, which functions in concert with other TCF target genes to promote growth and/or survival of cancer cells with defects in β-catenin regulation.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>12086873</pmid><doi>10.1016/S1535-6108(02)00035-1</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| language | eng |
| recordid | cdi_proquest_miscellaneous_71859695 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete; Cell Press Free Archives; EZB-FREE-00999 freely available EZB journals |
| subjects | Animals beta Catenin Cell Transformation, Neoplastic - genetics Cell Transformation, Neoplastic - metabolism Cytoskeletal Proteins - genetics Cytoskeletal Proteins - metabolism DNA-Binding Proteins - metabolism Female Humans Lymphoid Enhancer-Binding Factor 1 Mutation - genetics Neoplasms - metabolism Ovarian Neoplasms - metabolism Ovarian Neoplasms - pathology Proto-Oncogene Proteins - metabolism Rats Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics RNA, Messenger - metabolism Signal Transduction TCF Transcription Factors Trans-Activators - metabolism Transcription Factor 4 Transcription Factor 7-Like 2 Protein Transcription Factors - metabolism Tumor Cells, Cultured Wnt Proteins Zebrafish Proteins |
| title | ITF-2, a downstream target of the Wnt/TCF pathway, is activated in human cancers with β-catenin defects and promotes neoplastic transformation |
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