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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The <italic>Cdx2</italic> homeobox gene has a tumour suppressor function in the distal colon in addition to a homeotic role during gut development</title><author><name sortKey="Bonhomme, C" sort="Bonhomme, C" uniqKey="Bonhomme C" first="C" last="Bonhomme">C. Bonhomme</name><affiliation><nlm:aff id="aff1">Inserm, Unit 381, 3 Ave Molière, 67200 Strasbourg, France</nlm:aff></affiliation></author><author><name sortKey="Duluc, I" sort="Duluc, I" uniqKey="Duluc I" first="I" last="Duluc">I. Duluc</name><affiliation><nlm:aff id="aff1">Inserm, Unit 381, 3 Ave Molière, 67200 Strasbourg, France</nlm:aff></affiliation></author><author><name sortKey="Martin, E" sort="Martin, E" uniqKey="Martin E" first="E" last="Martin">E. Martin</name><affiliation><nlm:aff id="aff1">Inserm, Unit 381, 3 Ave Molière, 67200 Strasbourg, France</nlm:aff></affiliation></author><author><name sortKey="Chawengsaksophak, K" sort="Chawengsaksophak, K" uniqKey="Chawengsaksophak K" first="K" last="Chawengsaksophak">K. Chawengsaksophak</name><affiliation><nlm:aff id="aff2">Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria 3052, Australia</nlm:aff></affiliation></author><author><name sortKey="Chenard, M P" sort="Chenard, M P" uniqKey="Chenard M" first="M-P" last="Chenard">M-P Chenard</name><affiliation><nlm:aff id="aff3">Centre Hospitalier Universitaire de Strasbourg-Hautepierre, 67200 Strasbourg, France</nlm:aff></affiliation></author><author><name sortKey="Kedinger, M" sort="Kedinger, M" uniqKey="Kedinger M" first="M" last="Kedinger">M. Kedinger</name><affiliation><nlm:aff id="aff1">Inserm, Unit 381, 3 Ave Molière, 67200 Strasbourg, France</nlm:aff></affiliation></author><author><name sortKey="Beck, F" sort="Beck, F" uniqKey="Beck F" first="F" last="Beck">F. Beck</name><affiliation><nlm:aff id="aff4">Biochemistry Department, University of Leicester, University Rd, Leicester LE1 7RH, UK</nlm:aff></affiliation></author><author><name sortKey="Freund, J N" sort="Freund, J N" uniqKey="Freund J" first="J-N" last="Freund">J-N Freund</name><affiliation><nlm:aff id="aff1">Inserm, Unit 381, 3 Ave Molière, 67200 Strasbourg, France</nlm:aff></affiliation></author><author><name sortKey="Domon Dell, C" sort="Domon Dell, C" uniqKey="Domon Dell C" first="C" last="Domon-Dell">C. Domon-Dell</name><affiliation><nlm:aff id="aff1">Inserm, Unit 381, 3 Ave Molière, 67200 Strasbourg, France</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">12970140</idno><idno type="pmc">1773830</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1773830</idno><idno type="RBID">PMC:1773830</idno><date when="2003">2003</date><idno type="wicri:Area/Pmc/Corpus">000F82</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000F82</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The <italic>Cdx2</italic> homeobox gene has a tumour suppressor function in the distal colon in addition to a homeotic role during gut development</title><author><name sortKey="Bonhomme, C" sort="Bonhomme, C" uniqKey="Bonhomme C" first="C" last="Bonhomme">C. Bonhomme</name><affiliation><nlm:aff id="aff1">Inserm, Unit 381, 3 Ave Molière, 67200 Strasbourg, France</nlm:aff></affiliation></author><author><name sortKey="Duluc, I" sort="Duluc, I" uniqKey="Duluc I" first="I" last="Duluc">I. Duluc</name><affiliation><nlm:aff id="aff1">Inserm, Unit 381, 3 Ave Molière, 67200 Strasbourg, France</nlm:aff></affiliation></author><author><name sortKey="Martin, E" sort="Martin, E" uniqKey="Martin E" first="E" last="Martin">E. Martin</name><affiliation><nlm:aff id="aff1">Inserm, Unit 381, 3 Ave Molière, 67200 Strasbourg, France</nlm:aff></affiliation></author><author><name sortKey="Chawengsaksophak, K" sort="Chawengsaksophak, K" uniqKey="Chawengsaksophak K" first="K" last="Chawengsaksophak">K. Chawengsaksophak</name><affiliation><nlm:aff id="aff2">Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria 3052, Australia</nlm:aff></affiliation></author><author><name sortKey="Chenard, M P" sort="Chenard, M P" uniqKey="Chenard M" first="M-P" last="Chenard">M-P Chenard</name><affiliation><nlm:aff id="aff3">Centre Hospitalier Universitaire de Strasbourg-Hautepierre, 67200 Strasbourg, France</nlm:aff></affiliation></author><author><name sortKey="Kedinger, M" sort="Kedinger, M" uniqKey="Kedinger M" first="M" last="Kedinger">M. Kedinger</name><affiliation><nlm:aff id="aff1">Inserm, Unit 381, 3 Ave Molière, 67200 Strasbourg, France</nlm:aff></affiliation></author><author><name sortKey="Beck, F" sort="Beck, F" uniqKey="Beck F" first="F" last="Beck">F. Beck</name><affiliation><nlm:aff id="aff4">Biochemistry Department, University of Leicester, University Rd, Leicester LE1 7RH, UK</nlm:aff></affiliation></author><author><name sortKey="Freund, J N" sort="Freund, J N" uniqKey="Freund J" first="J-N" last="Freund">J-N Freund</name><affiliation><nlm:aff id="aff1">Inserm, Unit 381, 3 Ave Molière, 67200 Strasbourg, France</nlm:aff></affiliation></author><author><name sortKey="Domon Dell, C" sort="Domon Dell, C" uniqKey="Domon Dell C" first="C" last="Domon-Dell">C. Domon-Dell</name><affiliation><nlm:aff id="aff1">Inserm, Unit 381, 3 Ave Molière, 67200 Strasbourg, France</nlm:aff></affiliation></author></analytic><series><title level="j">Gut</title><idno type="ISSN">0017-5749</idno><idno type="eISSN">1458-3288</idno><imprint><date when="2003">2003</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Background:</bold> During development, the homeobox gene <italic>Cdx2</italic> exerts a homeotic function, providing the positional information necessary for correct specification of the midgut endoderm. This is illustrated by the non-neoplastic gastric-type heteroplasias present at birth in the pericaecal region of <italic>Cdx2<sup>+/−</sup></italic> mice. Furthermore, intestinal expression of <italic>Cdx2</italic> continues throughout life but diminishes in colorectal cancers compared with adjacent normal tissue, suggesting a role in tumorigenesis.</p><p><bold>Aim:</bold> To investigate the consequence of altered <italic>Cdx2</italic> expression on colon tumour initiation and/or progression.</p><p><bold>Methods:</bold> Heterozygous <italic>Cdx2<sup>+/−</sup></italic> mice were analysed for spontaneous malignant tumours and for tumour development after treatment with a DNA mutagen, azoxymethane.</p><p><bold>Results:</bold> <italic>Cdx2<sup>+/−</sup></italic> mice did not spontaneously develop malignant tumours. After azoxymethane treatment, the gastric-like heteroplasias in the pericaecal region did not evolve into cancer indicating that they are not precancerous lesions. However, azoxymethane treated <italic>Cdx2<sup>+/−</sup></italic> mice developed tumours specifically in the distal colon 12 weeks after azoxymethane treatment whereas no tumours were found in wild-type littermates at this stage. Histopathological and molecular analyses indicated that these tumours were invasive adenocarcinomas that recapitulated the malignant sequence observed in the majority of sporadic colorectal cancers in human. In addition, we found that the colonic epithelium was less sensitive to radiation induced apoptosis in <italic>Cdx2<sup>+/−</sup></italic> than in wild-type mice.</p><p><bold>Conclusion:</bold> This study provides the first experimental evidence that <italic>Cdx2</italic> is a tumour suppressor gene involved in cancer progression in the distal colon. This action in adults is functionally and geographically distinct from its homeotic role during gut development.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Gut</journal-id><journal-id journal-id-type="publisher-id">gutjnl</journal-id><journal-title>Gut</journal-title><issn pub-type="ppub">0017-5749</issn><issn pub-type="epub">1458-3288</issn><publisher><publisher-name>Copyright 2003 by Gut</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">12970140</article-id><article-id pub-id-type="pmc">1773830</article-id><article-id pub-id-type="publisher-id">0521465</article-id><article-categories><subj-group subj-group-type="heading"><subject>Colon</subject></subj-group></article-categories><title-group><article-title>The <italic>Cdx2</italic> homeobox gene has a tumour suppressor function in the distal colon in addition to a homeotic role during gut development</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Bonhomme</surname><given-names>C</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="fn" rid="fn1">*</xref></contrib><contrib contrib-type="author"><name><surname>Duluc</surname><given-names>I</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="fn" rid="fn1">*</xref></contrib><contrib contrib-type="author"><name><surname>Martin</surname><given-names>E</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Chawengsaksophak</surname><given-names>K</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Chenard</surname><given-names>M-P</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Kedinger</surname><given-names>M</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Beck</surname><given-names>F</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Freund</surname><given-names>J-N</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Domon-Dell</surname><given-names>C</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib></contrib-group><aff id="aff1"><label>1</label>Inserm, Unit 381, 3 Ave Molière, 67200 Strasbourg, France</aff><aff id="aff2"><label>2</label>Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria 3052, Australia</aff><aff id="aff3"><label>3</label>Centre Hospitalier Universitaire de Strasbourg-Hautepierre, 67200 Strasbourg, France</aff><aff id="aff4"><label>4</label>Biochemistry Department, University of Leicester, University Rd, Leicester LE1 7RH, UK</aff><author-notes><fn id="fn1"><label>*</label><p>C Bonhomme and I Duluc contributed equally to this work.</p></fn><fn><p>Correspondence to:
J-N Freund, INSERM Unit 381, 3 Ave Molière, 67200 Strasbourg, France;
<email>jean-noel.freund@inserm.u-strasbg.fr</email></p></fn></author-notes><pub-date pub-type="ppub"><month>10</month><year>2003</year></pub-date><volume>52</volume><issue>10</issue><fpage>1465</fpage><lpage>1471</lpage><history><date date-type="accepted"><day>28</day><month>5</month><year>2003</year></date></history><copyright-statement>Copyright © Copyright 2003 by Gut</copyright-statement><copyright-year>2003</copyright-year><abstract><p><bold>Background:</bold> During development, the homeobox gene <italic>Cdx2</italic> exerts a homeotic function, providing the positional information necessary for correct specification of the midgut endoderm. This is illustrated by the non-neoplastic gastric-type heteroplasias present at birth in the pericaecal region of <italic>Cdx2<sup>+/−</sup></italic> mice. Furthermore, intestinal expression of <italic>Cdx2</italic> continues throughout life but diminishes in colorectal cancers compared with adjacent normal tissue, suggesting a role in tumorigenesis.</p><p><bold>Aim:</bold> To investigate the consequence of altered <italic>Cdx2</italic> expression on colon tumour initiation and/or progression.</p><p><bold>Methods:</bold> Heterozygous <italic>Cdx2<sup>+/−</sup></italic> mice were analysed for spontaneous malignant tumours and for tumour development after treatment with a DNA mutagen, azoxymethane.</p><p><bold>Results:</bold> <italic>Cdx2<sup>+/−</sup></italic> mice did not spontaneously develop malignant tumours. After azoxymethane treatment, the gastric-like heteroplasias in the pericaecal region did not evolve into cancer indicating that they are not precancerous lesions. However, azoxymethane treated <italic>Cdx2<sup>+/−</sup></italic> mice developed tumours specifically in the distal colon 12 weeks after azoxymethane treatment whereas no tumours were found in wild-type littermates at this stage. Histopathological and molecular analyses indicated that these tumours were invasive adenocarcinomas that recapitulated the malignant sequence observed in the majority of sporadic colorectal cancers in human. In addition, we found that the colonic epithelium was less sensitive to radiation induced apoptosis in <italic>Cdx2<sup>+/−</sup></italic> than in wild-type mice.</p><p><bold>Conclusion:</bold> This study provides the first experimental evidence that <italic>Cdx2</italic> is a tumour suppressor gene involved in cancer progression in the distal colon. This action in adults is functionally and geographically distinct from its homeotic role during gut development.</p></abstract><kwd-group><kwd>Cdx</kwd><kwd>azoxymethane</kwd><kwd>tumour progression</kwd><kwd>colon</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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