<?xml version="1.0" encoding="utf-8"?>
<TEI xmlns="http://www.tei-c.org/ns/1.0" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:hal="http://hal.archives-ouvertes.fr/" xmlns:gml="http://www.opengis.net/gml/3.3/" xmlns:gmlce="http://www.opengis.net/gml/3.3/ce" version="1.1" xsi:schemaLocation="http://www.tei-c.org/ns/1.0 http://api.archives-ouvertes.fr/documents/aofr-sword.xsd">
  <teiHeader>
    <fileDesc>
      <titleStmt>
        <title>HAL TEI export of hal-02905851</title>
      </titleStmt>
      <publicationStmt>
        <distributor>CCSD</distributor>
        <availability status="restricted">
          <licence target="https://creativecommons.org/publicdomain/zero/1.0/">CC0 1.0 - Universal</licence>
        </availability>
        <date when="2026-05-24T21:20:37+02:00"/>
      </publicationStmt>
      <sourceDesc>
        <p part="N">HAL API Platform</p>
      </sourceDesc>
    </fileDesc>
  </teiHeader>
  <text>
    <body>
      <listBibl>
        <biblFull>
          <titleStmt>
            <title xml:lang="en">A role for human MUC4 mucin gene, the ErbB2 ligand, as a target of TGF-b in pancreatic carcinogenesis</title>
            <author role="aut">
              <persName>
                <forename type="first">Nicolas</forename>
                <surname>Jonckheere</surname>
              </persName>
              <email type="md5">b90c5f7bca714c62f2ba98b8e7c94b4c</email>
              <email type="domain">inserm.fr</email>
              <idno type="idhal" notation="string">nicolasjonckheere</idno>
              <idno type="idhal" notation="numeric">740009</idno>
              <idno type="halauthorid" notation="string">17742-740009</idno>
              <idno type="ORCID">https://orcid.org/0000-0002-0496-0661</idno>
              <idno type="IDREF">https://www.idref.fr/094282153</idno>
              <affiliation ref="#struct-545691"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Michael</forename>
                <surname>Perrais</surname>
              </persName>
              <idno type="halauthorid">1417749-0</idno>
              <affiliation ref="#struct-545691"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Christophe</forename>
                <surname>Mariette</surname>
              </persName>
              <idno type="halauthorid">119025-0</idno>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Surinder</forename>
                <forename type="middle">K</forename>
                <surname>Batra</surname>
              </persName>
              <idno type="halauthorid">2036092-0</idno>
              <affiliation ref="#struct-158657"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Jean-Pierre</forename>
                <surname>Aubert</surname>
              </persName>
              <email type="md5">fc3f7e300813825618dae00a46be5534</email>
              <email type="domain">lille.inserm.fr</email>
              <idno type="idhal" notation="numeric">955073</idno>
              <idno type="halauthorid" notation="string">178304-955073</idno>
              <affiliation ref="#struct-303623"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Pascal</forename>
                <surname>Pigny</surname>
              </persName>
              <email type="md5">76528167d9a7cffa42555ea9b2a8ed6d</email>
              <email type="domain">lille.inserm.fr</email>
              <idno type="idhal" notation="numeric">841682</idno>
              <idno type="halauthorid" notation="string">220345-841682</idno>
              <affiliation ref="#struct-2919"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Isabelle</forename>
                <surname>van Seuningen</surname>
              </persName>
              <email type="md5">a38fa3f8c915378b8a7e4e039e4321cc</email>
              <email type="domain">inserm.fr</email>
              <idno type="idhal" notation="string">isabelle-van-seuningen</idno>
              <idno type="idhal" notation="numeric">179339</idno>
              <idno type="halauthorid" notation="string">4292-179339</idno>
              <idno type="RESEARCHERID">http://www.researcherid.com/rid/N-6176-2016</idno>
              <idno type="ORCID">https://orcid.org/0000-0002-3131-2694</idno>
              <idno type="IDREF">https://www.idref.fr/094282048</idno>
              <idno type="RESEARCHERID">http://www.researcherid.com/rid/http://www.researcherid.com/rid/N-6176-2016</idno>
              <affiliation ref="#struct-545691"/>
            </author>
            <editor role="depositor">
              <persName>
                <forename>ISABELLE</forename>
                <surname>VAN SEUNINGEN</surname>
              </persName>
              <email type="md5">a38fa3f8c915378b8a7e4e039e4321cc</email>
              <email type="domain">inserm.fr</email>
            </editor>
          </titleStmt>
          <editionStmt>
            <edition n="v1" type="current">
              <date type="whenSubmitted">2020-09-29 17:55:25</date>
              <date type="whenModified">2024-07-18 16:50:13</date>
              <date type="whenReleased">2020-09-30 15:11:26</date>
              <date type="whenProduced">2004</date>
              <date type="whenEndEmbargoed">2020-09-29</date>
              <ref type="file" target="https://hal.science/hal-02905851v1/document">
                <date notBefore="2020-09-29"/>
              </ref>
              <ref type="file" subtype="author" n="1" target="https://hal.science/hal-02905851v1/file/article.pdf" id="file-2905851-2601696">
                <date notBefore="2020-09-29"/>
              </ref>
              <ref type="externalLink" target="https://www.nature.com/articles/1207769.pdf"/>
            </edition>
            <respStmt>
              <resp>contributor</resp>
              <name key="692968">
                <persName>
                  <forename>ISABELLE</forename>
                  <surname>VAN SEUNINGEN</surname>
                </persName>
                <email type="md5">a38fa3f8c915378b8a7e4e039e4321cc</email>
                <email type="domain">inserm.fr</email>
              </name>
            </respStmt>
          </editionStmt>
          <publicationStmt>
            <distributor>CCSD</distributor>
            <idno type="halId">hal-02905851</idno>
            <idno type="halUri">https://hal.science/hal-02905851</idno>
            <idno type="halBibtex">jonckheere:hal-02905851</idno>
            <idno type="halRefHtml">&lt;i&gt;Oncogene&lt;/i&gt;, 2004, 23, pp.5729 - 5738. &lt;a target="_blank" href="https://dx.doi.org/10.1038/sj.onc.1207769"&gt;&amp;#x27E8;10.1038/sj.onc.1207769&amp;#x27E9;&lt;/a&gt;</idno>
            <idno type="halRef">Oncogene, 2004, 23, pp.5729 - 5738. &amp;#x27E8;10.1038/sj.onc.1207769&amp;#x27E9;</idno>
            <availability status="restricted">
              <licence target="https://about.hal.science/hal-authorisation-v1/">HAL Authorization<ref corresp="#file-2905851-2601696"/></licence>
            </availability>
          </publicationStmt>
          <seriesStmt>
            <idno type="stamp" n="UNIV-LILLE">Université de Lille</idno>
          </seriesStmt>
          <notesStmt>
            <note type="audience" n="2">International</note>
            <note type="popular" n="0">No</note>
            <note type="peer" n="1">Yes</note>
          </notesStmt>
          <sourceDesc>
            <biblStruct>
              <analytic>
                <title xml:lang="en">A role for human MUC4 mucin gene, the ErbB2 ligand, as a target of TGF-b in pancreatic carcinogenesis</title>
                <author role="aut">
                  <persName>
                    <forename type="first">Nicolas</forename>
                    <surname>Jonckheere</surname>
                  </persName>
                  <email type="md5">b90c5f7bca714c62f2ba98b8e7c94b4c</email>
                  <email type="domain">inserm.fr</email>
                  <idno type="idhal" notation="string">nicolasjonckheere</idno>
                  <idno type="idhal" notation="numeric">740009</idno>
                  <idno type="halauthorid" notation="string">17742-740009</idno>
                  <idno type="ORCID">https://orcid.org/0000-0002-0496-0661</idno>
                  <idno type="IDREF">https://www.idref.fr/094282153</idno>
                  <affiliation ref="#struct-545691"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Michael</forename>
                    <surname>Perrais</surname>
                  </persName>
                  <idno type="halauthorid">1417749-0</idno>
                  <affiliation ref="#struct-545691"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Christophe</forename>
                    <surname>Mariette</surname>
                  </persName>
                  <idno type="halauthorid">119025-0</idno>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Surinder</forename>
                    <forename type="middle">K</forename>
                    <surname>Batra</surname>
                  </persName>
                  <idno type="halauthorid">2036092-0</idno>
                  <affiliation ref="#struct-158657"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Jean-Pierre</forename>
                    <surname>Aubert</surname>
                  </persName>
                  <email type="md5">fc3f7e300813825618dae00a46be5534</email>
                  <email type="domain">lille.inserm.fr</email>
                  <idno type="idhal" notation="numeric">955073</idno>
                  <idno type="halauthorid" notation="string">178304-955073</idno>
                  <affiliation ref="#struct-303623"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Pascal</forename>
                    <surname>Pigny</surname>
                  </persName>
                  <email type="md5">76528167d9a7cffa42555ea9b2a8ed6d</email>
                  <email type="domain">lille.inserm.fr</email>
                  <idno type="idhal" notation="numeric">841682</idno>
                  <idno type="halauthorid" notation="string">220345-841682</idno>
                  <affiliation ref="#struct-2919"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Isabelle</forename>
                    <surname>van Seuningen</surname>
                  </persName>
                  <email type="md5">a38fa3f8c915378b8a7e4e039e4321cc</email>
                  <email type="domain">inserm.fr</email>
                  <idno type="idhal" notation="string">isabelle-van-seuningen</idno>
                  <idno type="idhal" notation="numeric">179339</idno>
                  <idno type="halauthorid" notation="string">4292-179339</idno>
                  <idno type="RESEARCHERID">http://www.researcherid.com/rid/N-6176-2016</idno>
                  <idno type="ORCID">https://orcid.org/0000-0002-3131-2694</idno>
                  <idno type="IDREF">https://www.idref.fr/094282048</idno>
                  <idno type="RESEARCHERID">http://www.researcherid.com/rid/http://www.researcherid.com/rid/N-6176-2016</idno>
                  <affiliation ref="#struct-545691"/>
                </author>
              </analytic>
              <monogr>
                <idno type="halJournalId" status="VALID">17619</idno>
                <idno type="issn">0950-9232</idno>
                <idno type="eissn">1476-5594</idno>
                <title level="j">Oncogene</title>
                <imprint>
                  <publisher>Nature Publishing Group [1987-....]</publisher>
                  <biblScope unit="volume">23</biblScope>
                  <biblScope unit="pp">5729 - 5738</biblScope>
                  <date type="datePub">2004</date>
                </imprint>
              </monogr>
              <idno type="doi">10.1038/sj.onc.1207769</idno>
            </biblStruct>
          </sourceDesc>
          <profileDesc>
            <langUsage>
              <language ident="en">English</language>
            </langUsage>
            <textClass>
              <keywords scheme="author">
                <term xml:lang="en">MUC4</term>
                <term xml:lang="en">pancreatic cancer</term>
                <term xml:lang="en">TGF-b</term>
                <term xml:lang="en">tran- scription</term>
                <term xml:lang="en">mucin</term>
                <term xml:lang="en">Smad4</term>
                <term xml:lang="en">acetylation</term>
              </keywords>
              <classCode scheme="halDomain" n="sdv">Life Sciences [q-bio]</classCode>
              <classCode scheme="halDomain" n="sdv.can">Life Sciences [q-bio]/Cancer</classCode>
              <classCode scheme="halTypology" n="ART">Journal articles</classCode>
              <classCode scheme="halOldTypology" n="ART">Journal articles</classCode>
              <classCode scheme="halTreeTypology" n="ART">Journal articles</classCode>
            </textClass>
            <abstract xml:lang="en">
              <p>MUC4 encodes a large transmembrane mucin that is overexpressed in pancreatic adenocarcinomas. The molecular mechanisms responsible for that altered pattern of expression are unknown. TGF-b, a pleiotropic cytokine, regulates numerous genes involved in pancreatic carcino-genesis via activation of the Smads proteins and MUC4 promoter is rich in Smad-binding elements. Our aim was to study whether the regulation of MUC4 expression by TGF-b in pancreatic cancer cells was strictly dependent on Smad4 activity. Three pancreatic cancer cell lines, CAPAN-1 (MUC4 þ /Smad4À), CAPAN-2 (MUC4 þ / Smad4 þ) and PANC-1 (MUC4À/Smad4 þ), were used. By RT-PCR, transfection assays and immunohistochem-istry, we show that (i) both MUC4 mRNA and apomucin expression are upregulated by TGF-b, (ii) Smad2 positively cooperates with Smad4 to activate the promoter , (iii) activation of Smad4 by exogenous TGF-b induces Smad4 binding to the promoter, (iv) Smad7 and c-ski both inhibit activation by Smad4. When Smad4 is mutated and inactive, TGF-b activates MUC4 expression via MAPK, PI3K and PKA signaling pathways. Absence of expression in PANC-1 cells is due to histone deacetylation. Altogether, these results indicate that upregulation of MUC4 by TGF-b is restricted to well-differentiated pancreatic cancer cells, and point out a novel mechanism for TGF-b as a key molecule in targeting MUC4 overexpression in pancreatic adenocarcinomas.</p>
            </abstract>
          </profileDesc>
        </biblFull>
      </listBibl>
    </body>
    <back>
      <listOrg type="structures">
        <org type="laboratory" xml:id="struct-545691" status="OLD">
          <idno type="RNSR">200716489X</idno>
          <orgName>Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837</orgName>
          <orgName type="acronym">JPArc</orgName>
          <date type="start">2007-01-01</date>
          <date type="end">2019-12-31</date>
          <desc>
            <address>
              <addrLine>Faculté de Médecine Henri Warembourg - Pôle Recherche - 1 place de verdun 59045 Lille cedex.</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://crjpa.fr/</ref>
          </desc>
          <listRelation>
            <relation active="#struct-164505" type="direct"/>
            <relation name="U1172" active="#struct-303623" type="direct"/>
            <relation name="U837" active="#struct-374570" type="direct"/>
          </listRelation>
        </org>
        <org type="laboratory" xml:id="struct-158657" status="INCOMING">
          <orgName>Department of Biochemistry and Molecular Biology</orgName>
          <desc>
            <address>
              <country key="US"/>
            </address>
          </desc>
          <listRelation>
            <relation active="#struct-302687" type="direct"/>
            <relation active="#struct-566542" type="indirect"/>
          </listRelation>
        </org>
        <org type="institution" xml:id="struct-303623" status="VALID">
          <idno type="IdRef">026388278</idno>
          <idno type="ROR">https://ror.org/02vjkv261</idno>
          <orgName>Institut National de la Santé et de la Recherche Médicale</orgName>
          <orgName type="acronym">INSERM</orgName>
          <desc>
            <address>
              <addrLine>101, rue de Tolbiac, 75013 Paris</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.inserm.fr</ref>
          </desc>
        </org>
        <org type="laboratory" xml:id="struct-2919" status="OLD">
          <orgName>Mucines Epitheliales : du Gene a la Fonction</orgName>
          <desc>
            <address>
              <addrLine>Batiment Inserm Gerard Biserte 1, Place de Verdun 59045 LILLE CEDEX</addrLine>
              <country key="FR"/>
            </address>
          </desc>
          <listRelation>
            <relation name="U560" active="#struct-303623" type="direct"/>
            <relation active="#struct-361611" type="direct"/>
          </listRelation>
        </org>
        <org type="institution" xml:id="struct-164505" status="OLD">
          <idno type="IdRef">144876604</idno>
          <idno type="ROR">https://ror.org/03btvgn05</idno>
          <orgName>Université Lille Nord de France (COMUE)</orgName>
          <date type="start">2015-01-01</date>
          <date type="end">2019-12-31</date>
          <desc>
            <address>
              <addrLine>COMUE Communauté d'universités et établissements Lille-Nord-de-France - - 365 bis, rue Jules Guesde BP 50458 - 59658 Villeneuve d’Ascq Cedex - (A succédé au PRES Université de Lille Nord de France)</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.cue-lillenorddefrance.fr/</ref>
          </desc>
        </org>
        <org type="regroupinstitution" xml:id="struct-374570" status="VALID">
          <idno type="IdRef">223446556</idno>
          <idno type="ISNI">0000 0001 2242 6780</idno>
          <idno type="ROR">https://ror.org/02kzqn938</idno>
          <idno type="Wikidata">Q3551621</idno>
          <orgName>Université de Lille</orgName>
          <desc>
            <address>
              <addrLine>EPE Université de Lille. -- 42 rue Paul Duez, 59000 Lille</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">https://www.univ-lille.fr/</ref>
          </desc>
        </org>
        <org type="institution" xml:id="struct-302687" status="VALID">
          <idno type="ROR">https://ror.org/00thqtb16</idno>
          <orgName>University of Nebraska Medical Center</orgName>
          <desc>
            <address>
              <addrLine>42nd and Emile, Omaha, Nebraska 68198, USA</addrLine>
              <country key="US"/>
            </address>
            <ref type="url">https://unmc.edu/</ref>
          </desc>
          <listRelation>
            <relation active="#struct-566542" type="direct"/>
          </listRelation>
        </org>
        <org type="regroupinstitution" xml:id="struct-566542" status="VALID">
          <orgName>University of Nebraska System</orgName>
          <desc>
            <address>
              <addrLine>Nebraska, USA</addrLine>
              <country key="US"/>
            </address>
            <ref type="url">https://nebraska.edu/</ref>
          </desc>
        </org>
        <org type="institution" xml:id="struct-361611" status="OLD">
          <idno type="IdRef">026404389</idno>
          <idno type="ISNI">0000000120977060</idno>
          <orgName>Université de Lille, Droit et Santé</orgName>
          <date type="end">2017-12-31</date>
          <desc>
            <address>
              <addrLine>42 rue Paul Duez 59000 Lille</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.univ-lille2.fr/</ref>
          </desc>
        </org>
      </listOrg>
    </back>
  </text>
</TEI>