A Soluble Dominant Negative Fibroblast Growth Factor Receptor 4 Isoform in Human MCF-7 Breast Cancer Cells
Fibroblast growth factor receptors (FGFRs) are receptor tyrosine kinases encoded by four closely related genes. FGFR 1, 2, and 3 have a number of isoforms derived by alternative splicing, alternative initiation and exon switching; however, FGFR4 has been reported to encode a single intact receptor w...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2001-09, Vol.287 (1), p.60-65 |
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| creator | Ezzat, Shereen Zheng, Lei Yu, ShunJiang Asa, Sylvia L. |
| description | Fibroblast growth factor receptors (FGFRs) are receptor tyrosine kinases encoded by four closely related genes. FGFR 1, 2, and 3 have a number of isoforms derived by alternative splicing, alternative initiation and exon switching; however, FGFR4 has been reported to encode a single intact receptor with three extracellular immunoglobulin (Ig)-like domains, a transmembrane domain, and a split intracellular kinase. Here we describe a novel C-terminally truncated soluble isoform of FGFR4 expressed by human epithelial breast cancer MCF-7 cells. This isoform results from failure of splicing of intron 4 resulting in an mRNA species that encodes an in-frame premature stop codon. Cells transfected with the corresponding cDNA containing intron 4 express a truncated releasable protein that is identified in conditioned media. This soluble FGFR4 isoform (sFGFR4) abrogates the effect of FGF-1-induced MAPK phosphorylation and PRL gene activation. These findings represent the first description of an endogenous soluble C-terminally truncated FGFR4 isoform with FGF modulatory properties. |
| doi_str_mv | 10.1006/bbrc.2001.5546 |
| format | Article |
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FGFR 1, 2, and 3 have a number of isoforms derived by alternative splicing, alternative initiation and exon switching; however, FGFR4 has been reported to encode a single intact receptor with three extracellular immunoglobulin (Ig)-like domains, a transmembrane domain, and a split intracellular kinase. Here we describe a novel C-terminally truncated soluble isoform of FGFR4 expressed by human epithelial breast cancer MCF-7 cells. This isoform results from failure of splicing of intron 4 resulting in an mRNA species that encodes an in-frame premature stop codon. Cells transfected with the corresponding cDNA containing intron 4 express a truncated releasable protein that is identified in conditioned media. This soluble FGFR4 isoform (sFGFR4) abrogates the effect of FGF-1-induced MAPK phosphorylation and PRL gene activation. These findings represent the first description of an endogenous soluble C-terminally truncated FGFR4 isoform with FGF modulatory properties.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1006/bbrc.2001.5546</identifier><identifier>PMID: 11549253</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>3T3 Cells ; Animals ; breast cancer ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Female ; FGF ; Fibroblast Growth Factor 1 ; Fibroblast Growth Factor 2 - metabolism ; fibroblast growth factor receptor 4 ; fibroblast growth factor receptor-4 isoforms ; Gene Deletion ; Humans ; Introns - genetics ; Mice ; Molecular Sequence Data ; PRL gene ; Protein Isoforms - genetics ; Protein Isoforms - metabolism ; Protein Isoforms - pharmacology ; Receptor, Fibroblast Growth Factor, Type 4 ; Receptors, Fibroblast Growth Factor - antagonists & inhibitors ; Receptors, Fibroblast Growth Factor - genetics ; Receptors, Fibroblast Growth Factor - metabolism ; RNA Splicing ; Solubility ; soluble dominant negative receptors ; Tumor Cells, Cultured</subject><ispartof>Biochemical and biophysical research communications, 2001-09, Vol.287 (1), p.60-65</ispartof><rights>2001 Academic Press</rights><rights>Copyright 2001 Academic Press.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c371t-8be66cb93c562d7fb9e30d144a2cea76f86711e7c815ae6dc1f12d6801acedc53</citedby><cites>FETCH-LOGICAL-c371t-8be66cb93c562d7fb9e30d144a2cea76f86711e7c815ae6dc1f12d6801acedc53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006291X01955469$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11549253$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ezzat, Shereen</creatorcontrib><creatorcontrib>Zheng, Lei</creatorcontrib><creatorcontrib>Yu, ShunJiang</creatorcontrib><creatorcontrib>Asa, Sylvia L.</creatorcontrib><title>A Soluble Dominant Negative Fibroblast Growth Factor Receptor 4 Isoform in Human MCF-7 Breast Cancer Cells</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Fibroblast growth factor receptors (FGFRs) are receptor tyrosine kinases encoded by four closely related genes. FGFR 1, 2, and 3 have a number of isoforms derived by alternative splicing, alternative initiation and exon switching; however, FGFR4 has been reported to encode a single intact receptor with three extracellular immunoglobulin (Ig)-like domains, a transmembrane domain, and a split intracellular kinase. Here we describe a novel C-terminally truncated soluble isoform of FGFR4 expressed by human epithelial breast cancer MCF-7 cells. This isoform results from failure of splicing of intron 4 resulting in an mRNA species that encodes an in-frame premature stop codon. Cells transfected with the corresponding cDNA containing intron 4 express a truncated releasable protein that is identified in conditioned media. This soluble FGFR4 isoform (sFGFR4) abrogates the effect of FGF-1-induced MAPK phosphorylation and PRL gene activation. These findings represent the first description of an endogenous soluble C-terminally truncated FGFR4 isoform with FGF modulatory properties.</description><subject>3T3 Cells</subject><subject>Animals</subject><subject>breast cancer</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Female</subject><subject>FGF</subject><subject>Fibroblast Growth Factor 1</subject><subject>Fibroblast Growth Factor 2 - metabolism</subject><subject>fibroblast growth factor receptor 4</subject><subject>fibroblast growth factor receptor-4 isoforms</subject><subject>Gene Deletion</subject><subject>Humans</subject><subject>Introns - genetics</subject><subject>Mice</subject><subject>Molecular Sequence Data</subject><subject>PRL gene</subject><subject>Protein Isoforms - genetics</subject><subject>Protein Isoforms - metabolism</subject><subject>Protein Isoforms - pharmacology</subject><subject>Receptor, Fibroblast Growth Factor, Type 4</subject><subject>Receptors, Fibroblast Growth Factor - antagonists & inhibitors</subject><subject>Receptors, Fibroblast Growth Factor - genetics</subject><subject>Receptors, Fibroblast Growth Factor - metabolism</subject><subject>RNA Splicing</subject><subject>Solubility</subject><subject>soluble dominant negative receptors</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>eNqFkUtLxDAUhYMoOj62LiUrdx1z-0jbpVZHBR_gA9yFJL3VSNuMSav4702ZAVfiKnfxnUM4HyGHwObAGD9Ryul5zBjMsyzlG2QGrGRRDCzdJDMWiCgu4WWH7Hr_HihIeblNdgCytIyzZEbeT-mjbUfVIj23nellP9A7fJWD-US6MMpZ1Uo_0Etnv4Y3upB6sI4-oMbldKT02tvGuo6anl6NnezpbbWIcnrmcIpVstfoaIVt6_fJViNbjwfrd488Ly6eqqvo5v7yujq9iXSSwxAVCjnXqkx0xuM6b1SJCashTWWsUea8KXgOgLkuIJPIaw0NxDUvGEiNtc6SPXK86l06-zGiH0RnvA4_kD3a0YuQTkuewL8g5EXJ4iwP4HwFame9d9iIpTOddN8CmJg0iEmDmDSISUMIHK2bR9Vh_Yuvdw9AsQIwDPFp0AmvDYatauNQD6K25q_uH3lWlec</recordid><startdate>20010914</startdate><enddate>20010914</enddate><creator>Ezzat, Shereen</creator><creator>Zheng, Lei</creator><creator>Yu, ShunJiang</creator><creator>Asa, Sylvia L.</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>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20010914</creationdate><title>A Soluble Dominant Negative Fibroblast Growth Factor Receptor 4 Isoform in Human MCF-7 Breast Cancer Cells</title><author>Ezzat, Shereen ; Zheng, Lei ; Yu, ShunJiang ; Asa, Sylvia L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c371t-8be66cb93c562d7fb9e30d144a2cea76f86711e7c815ae6dc1f12d6801acedc53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>3T3 Cells</topic><topic>Animals</topic><topic>breast cancer</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - pathology</topic><topic>Female</topic><topic>FGF</topic><topic>Fibroblast Growth Factor 1</topic><topic>Fibroblast Growth Factor 2 - metabolism</topic><topic>fibroblast growth factor receptor 4</topic><topic>fibroblast growth factor receptor-4 isoforms</topic><topic>Gene Deletion</topic><topic>Humans</topic><topic>Introns - genetics</topic><topic>Mice</topic><topic>Molecular Sequence Data</topic><topic>PRL gene</topic><topic>Protein Isoforms - genetics</topic><topic>Protein Isoforms - metabolism</topic><topic>Protein Isoforms - pharmacology</topic><topic>Receptor, Fibroblast Growth Factor, Type 4</topic><topic>Receptors, Fibroblast Growth Factor - antagonists & inhibitors</topic><topic>Receptors, Fibroblast Growth Factor - genetics</topic><topic>Receptors, Fibroblast Growth Factor - metabolism</topic><topic>RNA Splicing</topic><topic>Solubility</topic><topic>soluble dominant negative receptors</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ezzat, Shereen</creatorcontrib><creatorcontrib>Zheng, Lei</creatorcontrib><creatorcontrib>Yu, ShunJiang</creatorcontrib><creatorcontrib>Asa, Sylvia L.</creatorcontrib><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><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ezzat, Shereen</au><au>Zheng, Lei</au><au>Yu, ShunJiang</au><au>Asa, Sylvia L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Soluble Dominant Negative Fibroblast Growth Factor Receptor 4 Isoform in Human MCF-7 Breast Cancer Cells</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2001-09-14</date><risdate>2001</risdate><volume>287</volume><issue>1</issue><spage>60</spage><epage>65</epage><pages>60-65</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Fibroblast growth factor receptors (FGFRs) are receptor tyrosine kinases encoded by four closely related genes. FGFR 1, 2, and 3 have a number of isoforms derived by alternative splicing, alternative initiation and exon switching; however, FGFR4 has been reported to encode a single intact receptor with three extracellular immunoglobulin (Ig)-like domains, a transmembrane domain, and a split intracellular kinase. Here we describe a novel C-terminally truncated soluble isoform of FGFR4 expressed by human epithelial breast cancer MCF-7 cells. This isoform results from failure of splicing of intron 4 resulting in an mRNA species that encodes an in-frame premature stop codon. Cells transfected with the corresponding cDNA containing intron 4 express a truncated releasable protein that is identified in conditioned media. This soluble FGFR4 isoform (sFGFR4) abrogates the effect of FGF-1-induced MAPK phosphorylation and PRL gene activation. 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| subjects | 3T3 Cells Animals breast cancer Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - pathology Female FGF Fibroblast Growth Factor 1 Fibroblast Growth Factor 2 - metabolism fibroblast growth factor receptor 4 fibroblast growth factor receptor-4 isoforms Gene Deletion Humans Introns - genetics Mice Molecular Sequence Data PRL gene Protein Isoforms - genetics Protein Isoforms - metabolism Protein Isoforms - pharmacology Receptor, Fibroblast Growth Factor, Type 4 Receptors, Fibroblast Growth Factor - antagonists & inhibitors Receptors, Fibroblast Growth Factor - genetics Receptors, Fibroblast Growth Factor - metabolism RNA Splicing Solubility soluble dominant negative receptors Tumor Cells, Cultured |
| title | A Soluble Dominant Negative Fibroblast Growth Factor Receptor 4 Isoform in Human MCF-7 Breast Cancer Cells |
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