Gene Expression Profiling Leads to Identification of GLI1-binding Elements in Target Genes and a Role for Multiple Downstream Pathways in GLI1-induced Cell Transformation
The zinc finger transcription factor GLI1, which mediates Sonic hedgehog signaling during development, is expressed in several human cancers, including basal cell carcinoma, medulloblastoma, and sarcomas. We identified 147 genes whose levels of expression were significantly altered in RNA obtained f...
Gespeichert in:
| Veröffentlicht in: | The Journal of biological chemistry 2002-02, Vol.277 (7), p.5548-5555 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 5555 |
|---|---|
| container_issue | 7 |
| container_start_page | 5548 |
| container_title | The Journal of biological chemistry |
| container_volume | 277 |
| creator | Yoon, Joon Won Kita, Yasuhiro Frank, Daniel J Majewski, Rebecca R Konicek, Beth A Nobrega, Marcelo A Jacob, Howard Walterhouse, David Iannaccone, Philip |
| description | The zinc finger transcription factor GLI1, which mediates Sonic hedgehog signaling during development, is expressed in several
human cancers, including basal cell carcinoma, medulloblastoma, and sarcomas. We identified 147 genes whose levels of expression
were significantly altered in RNA obtained from cells demonstrating a transformed phenotype with stable GLI1 expression or stable Ha-ras expression. Comparison of expression profiles from GLI1- and Ha-ras -expressing cells established a set of genes unique to GLI1 -induced cell transformation. Thirty genes were altered by stable GLI1 expression, and 124 genes were changed by stable Ha-ras expression. Seven genes had altered expression levels in both GLI1- and Ha-ras -expressing cells. Genes whose expression was altered by GLI1 included cell cycle genes, cell adhesion genes, signal transduction genes, and genes regulating apoptosis. GLI1 consensus
DNA-binding sequences were identified in the 5â² regions of cyclin D2, IGFBP-6 , osteopontin, and plakoglobin, suggesting that these genes represent immediate downstream targets. Gel shift analysis confirmed
the ability of the GLI1 protein to bind these sequences. Up-regulation of cyclin D2 and down-regulation of plakoglobin were
demonstrated in GLI1 -amplified compared with non-amplified human rhabdomyosarcoma cells. Many of the GLI1 targets with known function identified in this study increase cell proliferation, indicating that GLI1 -induced cell transformation occurs through multiple downstream pathways. |
| doi_str_mv | 10.1074/jbc.M105708200 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_71449116</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>71449116</sourcerecordid><originalsourceid>FETCH-LOGICAL-c455t-523307565abce69f7cda613d18d1c5a0b37319a4f1e4fbf36a16ace1eba23b833</originalsourceid><addsrcrecordid>eNqFkU-LEzEYh4Mobl29epTgwdvUvJPJ_DlKt9ZCFxep4C1kMm_aLDNJTabU_Up-SjNtYY_mEgLP78nL-yPkPbA5sKr4_Njq-T0wUbE6Z-wFmQGrecYF_HpJZozlkDW5qG_ImxgfWTpFA6_JDUAFjWDljPxdoUO6_HMIGKP1jj4Eb2xv3Y5uUHWRjp6uO3SjNVarcSK8oavNGrLWum7ilj0OCYjUOrpVYYcjnaSRKtdRRX_4Hqnxgd4f-9Ee0uPOn1wcA6qBPqhxf1JP5-xZmpxHjR1dYN_TbVAupuhw_vgteWVUH_Hd9b4lP78ut4tv2eb7ar34ssl0IcSYiZxzVolSqFZj2ZhKd6oE3kHdgRaKtbzi0KjCABamNbxUUCqNgK3KeVtzfks-XbyH4H8fMY5ysFGneZRDf4yygiJtEcr_glCn1TM-gfMLqIOPMaCRh2AHFZ4kMDnVKFON8rnGFPhwNR_bAbtn_NpbAj5egL3d7U82oGyt13scZF5VspJCFDX_B1mppfM</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>18258036</pqid></control><display><type>article</type><title>Gene Expression Profiling Leads to Identification of GLI1-binding Elements in Target Genes and a Role for Multiple Downstream Pathways in GLI1-induced Cell Transformation</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Yoon, Joon Won ; Kita, Yasuhiro ; Frank, Daniel J ; Majewski, Rebecca R ; Konicek, Beth A ; Nobrega, Marcelo A ; Jacob, Howard ; Walterhouse, David ; Iannaccone, Philip</creator><creatorcontrib>Yoon, Joon Won ; Kita, Yasuhiro ; Frank, Daniel J ; Majewski, Rebecca R ; Konicek, Beth A ; Nobrega, Marcelo A ; Jacob, Howard ; Walterhouse, David ; Iannaccone, Philip</creatorcontrib><description>The zinc finger transcription factor GLI1, which mediates Sonic hedgehog signaling during development, is expressed in several
human cancers, including basal cell carcinoma, medulloblastoma, and sarcomas. We identified 147 genes whose levels of expression
were significantly altered in RNA obtained from cells demonstrating a transformed phenotype with stable GLI1 expression or stable Ha-ras expression. Comparison of expression profiles from GLI1- and Ha-ras -expressing cells established a set of genes unique to GLI1 -induced cell transformation. Thirty genes were altered by stable GLI1 expression, and 124 genes were changed by stable Ha-ras expression. Seven genes had altered expression levels in both GLI1- and Ha-ras -expressing cells. Genes whose expression was altered by GLI1 included cell cycle genes, cell adhesion genes, signal transduction genes, and genes regulating apoptosis. GLI1 consensus
DNA-binding sequences were identified in the 5â² regions of cyclin D2, IGFBP-6 , osteopontin, and plakoglobin, suggesting that these genes represent immediate downstream targets. Gel shift analysis confirmed
the ability of the GLI1 protein to bind these sequences. Up-regulation of cyclin D2 and down-regulation of plakoglobin were
demonstrated in GLI1 -amplified compared with non-amplified human rhabdomyosarcoma cells. Many of the GLI1 targets with known function identified in this study increase cell proliferation, indicating that GLI1 -induced cell transformation occurs through multiple downstream pathways.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M105708200</identifier><identifier>PMID: 11719506</identifier><language>eng</language><publisher>United States: American Society for Biochemistry and Molecular Biology</publisher><subject>Amino Acid Motifs ; Animals ; Apoptosis ; Base Sequence ; Biotinylation ; Blotting, Northern ; Cell Adhesion ; Cell Line, Transformed ; Cyclin D2 ; Cyclins - biosynthesis ; Cytoskeletal Proteins - biosynthesis ; Desmoplakins ; DNA, Complementary - metabolism ; Down-Regulation ; gamma Catenin ; GLI1 protein ; Ha-ras gene ; Humans ; In Situ Hybridization ; Insulin-Like Growth Factor Binding Protein 6 - biosynthesis ; Models, Biological ; Molecular Sequence Data ; Oligonucleotide Array Sequence Analysis ; Oncogene Proteins - biosynthesis ; Oncogene Proteins - genetics ; Osteopontin ; Phenotype ; plakoglobin ; Protein Binding ; Protein Structure, Tertiary ; ras Proteins - biosynthesis ; Rats ; Recombinant Fusion Proteins - metabolism ; Rhabdomyosarcoma - metabolism ; RNA - metabolism ; RNA, Messenger - metabolism ; Sialoglycoproteins - biosynthesis ; Signal Transduction ; Trans-Activators ; Transcription Factors - biosynthesis ; Transcription Factors - genetics ; Tumor Cells, Cultured ; Up-Regulation ; Zinc Finger Protein GLI1</subject><ispartof>The Journal of biological chemistry, 2002-02, Vol.277 (7), p.5548-5555</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-523307565abce69f7cda613d18d1c5a0b37319a4f1e4fbf36a16ace1eba23b833</citedby><cites>FETCH-LOGICAL-c455t-523307565abce69f7cda613d18d1c5a0b37319a4f1e4fbf36a16ace1eba23b833</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11719506$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yoon, Joon Won</creatorcontrib><creatorcontrib>Kita, Yasuhiro</creatorcontrib><creatorcontrib>Frank, Daniel J</creatorcontrib><creatorcontrib>Majewski, Rebecca R</creatorcontrib><creatorcontrib>Konicek, Beth A</creatorcontrib><creatorcontrib>Nobrega, Marcelo A</creatorcontrib><creatorcontrib>Jacob, Howard</creatorcontrib><creatorcontrib>Walterhouse, David</creatorcontrib><creatorcontrib>Iannaccone, Philip</creatorcontrib><title>Gene Expression Profiling Leads to Identification of GLI1-binding Elements in Target Genes and a Role for Multiple Downstream Pathways in GLI1-induced Cell Transformation</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>The zinc finger transcription factor GLI1, which mediates Sonic hedgehog signaling during development, is expressed in several
human cancers, including basal cell carcinoma, medulloblastoma, and sarcomas. We identified 147 genes whose levels of expression
were significantly altered in RNA obtained from cells demonstrating a transformed phenotype with stable GLI1 expression or stable Ha-ras expression. Comparison of expression profiles from GLI1- and Ha-ras -expressing cells established a set of genes unique to GLI1 -induced cell transformation. Thirty genes were altered by stable GLI1 expression, and 124 genes were changed by stable Ha-ras expression. Seven genes had altered expression levels in both GLI1- and Ha-ras -expressing cells. Genes whose expression was altered by GLI1 included cell cycle genes, cell adhesion genes, signal transduction genes, and genes regulating apoptosis. GLI1 consensus
DNA-binding sequences were identified in the 5â² regions of cyclin D2, IGFBP-6 , osteopontin, and plakoglobin, suggesting that these genes represent immediate downstream targets. Gel shift analysis confirmed
the ability of the GLI1 protein to bind these sequences. Up-regulation of cyclin D2 and down-regulation of plakoglobin were
demonstrated in GLI1 -amplified compared with non-amplified human rhabdomyosarcoma cells. Many of the GLI1 targets with known function identified in this study increase cell proliferation, indicating that GLI1 -induced cell transformation occurs through multiple downstream pathways.</description><subject>Amino Acid Motifs</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Base Sequence</subject><subject>Biotinylation</subject><subject>Blotting, Northern</subject><subject>Cell Adhesion</subject><subject>Cell Line, Transformed</subject><subject>Cyclin D2</subject><subject>Cyclins - biosynthesis</subject><subject>Cytoskeletal Proteins - biosynthesis</subject><subject>Desmoplakins</subject><subject>DNA, Complementary - metabolism</subject><subject>Down-Regulation</subject><subject>gamma Catenin</subject><subject>GLI1 protein</subject><subject>Ha-ras gene</subject><subject>Humans</subject><subject>In Situ Hybridization</subject><subject>Insulin-Like Growth Factor Binding Protein 6 - biosynthesis</subject><subject>Models, Biological</subject><subject>Molecular Sequence Data</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Oncogene Proteins - biosynthesis</subject><subject>Oncogene Proteins - genetics</subject><subject>Osteopontin</subject><subject>Phenotype</subject><subject>plakoglobin</subject><subject>Protein Binding</subject><subject>Protein Structure, Tertiary</subject><subject>ras Proteins - biosynthesis</subject><subject>Rats</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Rhabdomyosarcoma - metabolism</subject><subject>RNA - metabolism</subject><subject>RNA, Messenger - metabolism</subject><subject>Sialoglycoproteins - biosynthesis</subject><subject>Signal Transduction</subject><subject>Trans-Activators</subject><subject>Transcription Factors - biosynthesis</subject><subject>Transcription Factors - genetics</subject><subject>Tumor Cells, Cultured</subject><subject>Up-Regulation</subject><subject>Zinc Finger Protein GLI1</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU-LEzEYh4Mobl29epTgwdvUvJPJ_DlKt9ZCFxep4C1kMm_aLDNJTabU_Up-SjNtYY_mEgLP78nL-yPkPbA5sKr4_Njq-T0wUbE6Z-wFmQGrecYF_HpJZozlkDW5qG_ImxgfWTpFA6_JDUAFjWDljPxdoUO6_HMIGKP1jj4Eb2xv3Y5uUHWRjp6uO3SjNVarcSK8oavNGrLWum7ilj0OCYjUOrpVYYcjnaSRKtdRRX_4Hqnxgd4f-9Ee0uPOn1wcA6qBPqhxf1JP5-xZmpxHjR1dYN_TbVAupuhw_vgteWVUH_Hd9b4lP78ut4tv2eb7ar34ssl0IcSYiZxzVolSqFZj2ZhKd6oE3kHdgRaKtbzi0KjCABamNbxUUCqNgK3KeVtzfks-XbyH4H8fMY5ysFGneZRDf4yygiJtEcr_glCn1TM-gfMLqIOPMaCRh2AHFZ4kMDnVKFON8rnGFPhwNR_bAbtn_NpbAj5egL3d7U82oGyt13scZF5VspJCFDX_B1mppfM</recordid><startdate>20020215</startdate><enddate>20020215</enddate><creator>Yoon, Joon Won</creator><creator>Kita, Yasuhiro</creator><creator>Frank, Daniel J</creator><creator>Majewski, Rebecca R</creator><creator>Konicek, Beth A</creator><creator>Nobrega, Marcelo A</creator><creator>Jacob, Howard</creator><creator>Walterhouse, David</creator><creator>Iannaccone, Philip</creator><general>American Society for Biochemistry and Molecular Biology</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>7TM</scope><scope>7X8</scope></search><sort><creationdate>20020215</creationdate><title>Gene Expression Profiling Leads to Identification of GLI1-binding Elements in Target Genes and a Role for Multiple Downstream Pathways in GLI1-induced Cell Transformation</title><author>Yoon, Joon Won ; Kita, Yasuhiro ; Frank, Daniel J ; Majewski, Rebecca R ; Konicek, Beth A ; Nobrega, Marcelo A ; Jacob, Howard ; Walterhouse, David ; Iannaccone, Philip</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-523307565abce69f7cda613d18d1c5a0b37319a4f1e4fbf36a16ace1eba23b833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Amino Acid Motifs</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Base Sequence</topic><topic>Biotinylation</topic><topic>Blotting, Northern</topic><topic>Cell Adhesion</topic><topic>Cell Line, Transformed</topic><topic>Cyclin D2</topic><topic>Cyclins - biosynthesis</topic><topic>Cytoskeletal Proteins - biosynthesis</topic><topic>Desmoplakins</topic><topic>DNA, Complementary - metabolism</topic><topic>Down-Regulation</topic><topic>gamma Catenin</topic><topic>GLI1 protein</topic><topic>Ha-ras gene</topic><topic>Humans</topic><topic>In Situ Hybridization</topic><topic>Insulin-Like Growth Factor Binding Protein 6 - biosynthesis</topic><topic>Models, Biological</topic><topic>Molecular Sequence Data</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Oncogene Proteins - biosynthesis</topic><topic>Oncogene Proteins - genetics</topic><topic>Osteopontin</topic><topic>Phenotype</topic><topic>plakoglobin</topic><topic>Protein Binding</topic><topic>Protein Structure, Tertiary</topic><topic>ras Proteins - biosynthesis</topic><topic>Rats</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Rhabdomyosarcoma - metabolism</topic><topic>RNA - metabolism</topic><topic>RNA, Messenger - metabolism</topic><topic>Sialoglycoproteins - biosynthesis</topic><topic>Signal Transduction</topic><topic>Trans-Activators</topic><topic>Transcription Factors - biosynthesis</topic><topic>Transcription Factors - genetics</topic><topic>Tumor Cells, Cultured</topic><topic>Up-Regulation</topic><topic>Zinc Finger Protein GLI1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yoon, Joon Won</creatorcontrib><creatorcontrib>Kita, Yasuhiro</creatorcontrib><creatorcontrib>Frank, Daniel J</creatorcontrib><creatorcontrib>Majewski, Rebecca R</creatorcontrib><creatorcontrib>Konicek, Beth A</creatorcontrib><creatorcontrib>Nobrega, Marcelo A</creatorcontrib><creatorcontrib>Jacob, Howard</creatorcontrib><creatorcontrib>Walterhouse, David</creatorcontrib><creatorcontrib>Iannaccone, Philip</creatorcontrib><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>MEDLINE - Academic</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yoon, Joon Won</au><au>Kita, Yasuhiro</au><au>Frank, Daniel J</au><au>Majewski, Rebecca R</au><au>Konicek, Beth A</au><au>Nobrega, Marcelo A</au><au>Jacob, Howard</au><au>Walterhouse, David</au><au>Iannaccone, Philip</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gene Expression Profiling Leads to Identification of GLI1-binding Elements in Target Genes and a Role for Multiple Downstream Pathways in GLI1-induced Cell Transformation</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2002-02-15</date><risdate>2002</risdate><volume>277</volume><issue>7</issue><spage>5548</spage><epage>5555</epage><pages>5548-5555</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>The zinc finger transcription factor GLI1, which mediates Sonic hedgehog signaling during development, is expressed in several
human cancers, including basal cell carcinoma, medulloblastoma, and sarcomas. We identified 147 genes whose levels of expression
were significantly altered in RNA obtained from cells demonstrating a transformed phenotype with stable GLI1 expression or stable Ha-ras expression. Comparison of expression profiles from GLI1- and Ha-ras -expressing cells established a set of genes unique to GLI1 -induced cell transformation. Thirty genes were altered by stable GLI1 expression, and 124 genes were changed by stable Ha-ras expression. Seven genes had altered expression levels in both GLI1- and Ha-ras -expressing cells. Genes whose expression was altered by GLI1 included cell cycle genes, cell adhesion genes, signal transduction genes, and genes regulating apoptosis. GLI1 consensus
DNA-binding sequences were identified in the 5â² regions of cyclin D2, IGFBP-6 , osteopontin, and plakoglobin, suggesting that these genes represent immediate downstream targets. Gel shift analysis confirmed
the ability of the GLI1 protein to bind these sequences. Up-regulation of cyclin D2 and down-regulation of plakoglobin were
demonstrated in GLI1 -amplified compared with non-amplified human rhabdomyosarcoma cells. Many of the GLI1 targets with known function identified in this study increase cell proliferation, indicating that GLI1 -induced cell transformation occurs through multiple downstream pathways.</abstract><cop>United States</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>11719506</pmid><doi>10.1074/jbc.M105708200</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9258 |
| ispartof | The Journal of biological chemistry, 2002-02, Vol.277 (7), p.5548-5555 |
| issn | 0021-9258 1083-351X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_71449116 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Amino Acid Motifs Animals Apoptosis Base Sequence Biotinylation Blotting, Northern Cell Adhesion Cell Line, Transformed Cyclin D2 Cyclins - biosynthesis Cytoskeletal Proteins - biosynthesis Desmoplakins DNA, Complementary - metabolism Down-Regulation gamma Catenin GLI1 protein Ha-ras gene Humans In Situ Hybridization Insulin-Like Growth Factor Binding Protein 6 - biosynthesis Models, Biological Molecular Sequence Data Oligonucleotide Array Sequence Analysis Oncogene Proteins - biosynthesis Oncogene Proteins - genetics Osteopontin Phenotype plakoglobin Protein Binding Protein Structure, Tertiary ras Proteins - biosynthesis Rats Recombinant Fusion Proteins - metabolism Rhabdomyosarcoma - metabolism RNA - metabolism RNA, Messenger - metabolism Sialoglycoproteins - biosynthesis Signal Transduction Trans-Activators Transcription Factors - biosynthesis Transcription Factors - genetics Tumor Cells, Cultured Up-Regulation Zinc Finger Protein GLI1 |
| title | Gene Expression Profiling Leads to Identification of GLI1-binding Elements in Target Genes and a Role for Multiple Downstream Pathways in GLI1-induced Cell Transformation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-13T14%3A54%3A18IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Gene%20Expression%20Profiling%20Leads%20to%20Identification%20of%20GLI1-binding%20Elements%20in%20Target%20Genes%20and%20a%20Role%20for%20Multiple%20Downstream%20Pathways%20in%20GLI1-induced%20Cell%20Transformation&rft.jtitle=The%20Journal%20of%20biological%20chemistry&rft.au=Yoon,%20Joon%20Won&rft.date=2002-02-15&rft.volume=277&rft.issue=7&rft.spage=5548&rft.epage=5555&rft.pages=5548-5555&rft.issn=0021-9258&rft.eissn=1083-351X&rft_id=info:doi/10.1074/jbc.M105708200&rft_dat=%3Cproquest_cross%3E71449116%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=18258036&rft_id=info:pmid/11719506&rfr_iscdi=true |