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<record>
<TEI>
<teiHeader>
<fileDesc>
<titleStmt>
<title xml:lang="en">Different Modalities of Intercellular Membrane Exchanges Mediate Cell-to-cell P-glycoprotein Transfers in MCF-7 Breast Cancer Cells
<xref ref-type="fn" rid="FN1">*</xref>
<xref ref-type="fn" rid="FN2">
<sup>
<inline-graphic xlink:href="sbox.jpg"></inline-graphic>
</sup>
</xref>
</title>
<author>
<name sortKey="Pasquier, Jennifer" sort="Pasquier, Jennifer" uniqKey="Pasquier J" first="Jennifer" last="Pasquier">Jennifer Pasquier</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">PRIMACEN, Cell Imaging Platform of Normandy, Inserm, Institute for Research and Innovation in Biomedicine (IRIB), University of Rouen, 76821 Mont-Saint-Aignan, France,</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Galas, Ludovic" sort="Galas, Ludovic" uniqKey="Galas L" first="Ludovic" last="Galas">Ludovic Galas</name>
<affiliation>
<nlm:aff id="aff2">PRIMACEN, Cell Imaging Platform of Normandy, Inserm, Institute for Research and Innovation in Biomedicine (IRIB), University of Rouen, 76821 Mont-Saint-Aignan, France,</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Boulange Lecomte, Celine" sort="Boulange Lecomte, Celine" uniqKey="Boulange Lecomte C" first="Céline" last="Boulangé-Lecomte">Céline Boulangé-Lecomte</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Rioult, Damien" sort="Rioult, Damien" uniqKey="Rioult D" first="Damien" last="Rioult">Damien Rioult</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Bultelle, Florence" sort="Bultelle, Florence" uniqKey="Bultelle F" first="Florence" last="Bultelle">Florence Bultelle</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Magal, Pierre" sort="Magal, Pierre" uniqKey="Magal P" first="Pierre" last="Magal">Pierre Magal</name>
<affiliation>
<nlm:aff wicri:cut=", and" id="aff3">UMR CNRS 5251 IMB and INRIA sud-ouest Anubis, University of Bordeaux, 33076 Bordeaux, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Webb, Glenn" sort="Webb, Glenn" uniqKey="Webb G" first="Glenn" last="Webb">Glenn Webb</name>
<affiliation>
<nlm:aff id="aff4"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Le Foll, Frank" sort="Le Foll, Frank" uniqKey="Le Foll F" first="Frank" last="Le Foll">Frank Le Foll</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
</titleStmt>
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<idno type="wicri:source">PMC</idno>
<idno type="pmid">22228759</idno>
<idno type="pmc">3293537</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3293537</idno>
<idno type="RBID">PMC:3293537</idno>
<idno type="doi">10.1074/jbc.M111.312157</idno>
<date when="2012">2012</date>
<idno type="wicri:Area/Pmc/Corpus">000185</idno>
</publicationStmt>
<sourceDesc>
<biblStruct>
<analytic>
<title xml:lang="en" level="a" type="main">Different Modalities of Intercellular Membrane Exchanges Mediate Cell-to-cell P-glycoprotein Transfers in MCF-7 Breast Cancer Cells
<xref ref-type="fn" rid="FN1">*</xref>
<xref ref-type="fn" rid="FN2">
<sup>
<inline-graphic xlink:href="sbox.jpg"></inline-graphic>
</sup>
</xref>
</title>
<author>
<name sortKey="Pasquier, Jennifer" sort="Pasquier, Jennifer" uniqKey="Pasquier J" first="Jennifer" last="Pasquier">Jennifer Pasquier</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">PRIMACEN, Cell Imaging Platform of Normandy, Inserm, Institute for Research and Innovation in Biomedicine (IRIB), University of Rouen, 76821 Mont-Saint-Aignan, France,</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Galas, Ludovic" sort="Galas, Ludovic" uniqKey="Galas L" first="Ludovic" last="Galas">Ludovic Galas</name>
<affiliation>
<nlm:aff id="aff2">PRIMACEN, Cell Imaging Platform of Normandy, Inserm, Institute for Research and Innovation in Biomedicine (IRIB), University of Rouen, 76821 Mont-Saint-Aignan, France,</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Boulange Lecomte, Celine" sort="Boulange Lecomte, Celine" uniqKey="Boulange Lecomte C" first="Céline" last="Boulangé-Lecomte">Céline Boulangé-Lecomte</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Rioult, Damien" sort="Rioult, Damien" uniqKey="Rioult D" first="Damien" last="Rioult">Damien Rioult</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Bultelle, Florence" sort="Bultelle, Florence" uniqKey="Bultelle F" first="Florence" last="Bultelle">Florence Bultelle</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Magal, Pierre" sort="Magal, Pierre" uniqKey="Magal P" first="Pierre" last="Magal">Pierre Magal</name>
<affiliation>
<nlm:aff wicri:cut=", and" id="aff3">UMR CNRS 5251 IMB and INRIA sud-ouest Anubis, University of Bordeaux, 33076 Bordeaux, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Webb, Glenn" sort="Webb, Glenn" uniqKey="Webb G" first="Glenn" last="Webb">Glenn Webb</name>
<affiliation>
<nlm:aff id="aff4"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Le Foll, Frank" sort="Le Foll, Frank" uniqKey="Le Foll F" first="Frank" last="Le Foll">Frank Le Foll</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
</analytic>
<series>
<title level="j">The Journal of Biological Chemistry</title>
<idno type="ISSN">0021-9258</idno>
<idno type="eISSN">1083-351X</idno>
<imprint>
<date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
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<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>
<bold>Background:</bold>
The P-glycoprotein is expressed in many human cancers, where it contributes to multi-drug resistance phenomenon.</p>
<p>
<bold>Results:</bold>
Both TnTs and microparticles contribute to the transfer of P-gp in MCF-7.</p>
<p>
<bold>Conclusion:</bold>
Our findings supply new mechanistic evidences for the extragenetic emergence of MDR in cancer cells.</p>
<p>
<bold>Significance:</bold>
Inhibition of both MPs and TnTs could be included in treatment strategies designed to overcome MDR.</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">J Biol Chem</journal-id>
<journal-id journal-id-type="hwp">jbc</journal-id>
<journal-id journal-id-type="pmc">jbc</journal-id>
<journal-id journal-id-type="publisher-id">JBC</journal-id>
<journal-title-group>
<journal-title>The Journal of Biological Chemistry</journal-title>
</journal-title-group>
<issn pub-type="ppub">0021-9258</issn>
<issn pub-type="epub">1083-351X</issn>
<publisher>
<publisher-name>American Society for Biochemistry and Molecular Biology</publisher-name>
<publisher-loc>9650 Rockville Pike, Bethesda, MD 20814, U.S.A.</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">22228759</article-id>
<article-id pub-id-type="pmc">3293537</article-id>
<article-id pub-id-type="publisher-id">M111.312157</article-id>
<article-id pub-id-type="doi">10.1074/jbc.M111.312157</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Cell Biology</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Different Modalities of Intercellular Membrane Exchanges Mediate Cell-to-cell P-glycoprotein Transfers in MCF-7 Breast Cancer Cells
<xref ref-type="fn" rid="FN1">*</xref>
<xref ref-type="fn" rid="FN2">
<sup>
<inline-graphic xlink:href="sbox.jpg"></inline-graphic>
</sup>
</xref>
</article-title>
<alt-title alt-title-type="short">Membrane Nanotubes and Microparticles Transfer P-gp in MCF-7</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Pasquier</surname>
<given-names>Jennifer</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup></sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>§</sup>
</xref>
<xref ref-type="author-notes" rid="FN3">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Galas</surname>
<given-names>Ludovic</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>§</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Boulangé-Lecomte</surname>
<given-names>Céline</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Rioult</surname>
<given-names>Damien</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bultelle</surname>
<given-names>Florence</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Magal</surname>
<given-names>Pierre</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Webb</surname>
<given-names>Glenn</given-names>
</name>
<xref ref-type="aff" rid="aff4">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Le Foll</surname>
<given-names>Frank</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup></sup>
</xref>
<xref ref-type="corresp" rid="cor1">
<sup>2</sup>
</xref>
</contrib>
<aff id="aff1">From the
<label></label>
Laboratory of Ecotoxicology, University of Le Havre, 76058 Le Havre, France,</aff>
<aff id="aff2">
<label>§</label>
PRIMACEN, Cell Imaging Platform of Normandy, Inserm, Institute for Research and Innovation in Biomedicine (IRIB), University of Rouen, 76821 Mont-Saint-Aignan, France,</aff>
<aff id="aff3">
<label></label>
UMR CNRS 5251 IMB and INRIA sud-ouest Anubis, University of Bordeaux, 33076 Bordeaux, France, and</aff>
<aff id="aff4">the
<label></label>
Department of Mathematics, Vanderbilt University, Stevenson Center, Nashville, Tennessee 37240</aff>
</contrib-group>
<author-notes>
<corresp id="cor1">
<label>2</label>
To whom correspondence should be addressed. E-mail:
<email>frank.lefoll@univ-lehavre.fr</email>
.</corresp>
<fn fn-type="other" id="FN3">
<label>1</label>
<p>Recipient of a fellowship from the Conseil Regional de Haute-Normandie.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub">
<day>2</day>
<month>3</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="epub">
<day>6</day>
<month>1</month>
<year>2012</year>
</pub-date>
<volume>287</volume>
<issue>10</issue>
<fpage>7374</fpage>
<lpage>7387</lpage>
<history>
<date date-type="received">
<day>12</day>
<month>10</month>
<year>2011</year>
</date>
<date date-type="rev-recd">
<day>13</day>
<month>12</month>
<year>2011</year>
</date>
</history>
<permissions>
<copyright-statement>© 2012 by The American Society for Biochemistry and Molecular Biology, Inc.</copyright-statement>
<copyright-year>2012</copyright-year>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zbc01012007374.pdf"></self-uri>
<abstract abstract-type="teaser">
<p>
<bold>Background:</bold>
The P-glycoprotein is expressed in many human cancers, where it contributes to multi-drug resistance phenomenon.</p>
<p>
<bold>Results:</bold>
Both TnTs and microparticles contribute to the transfer of P-gp in MCF-7.</p>
<p>
<bold>Conclusion:</bold>
Our findings supply new mechanistic evidences for the extragenetic emergence of MDR in cancer cells.</p>
<p>
<bold>Significance:</bold>
Inhibition of both MPs and TnTs could be included in treatment strategies designed to overcome MDR.</p>
</abstract>
<abstract>
<p>Multi-drug resistance (MDR) is a phenomenon by which tumor cells exhibit resistance to a variety of chemically unrelated chemotherapeutic drugs. The classical form of multidrug resistance is connected to overexpression of membrane P-glycoprotein (P-gp), which acts as an energy dependent drug efflux pump. P-glycoprotein expression is known to be controlled by genetic and epigenetic mechanisms. Until now processes of P-gp gene up-regulation and resistant cell selection were considered sufficient to explain the emergence of MDR phenotype within a cell population. Recently, however, “non-genetic” acquisitions of MDR by cell-to-cell P-gp transfers have been pointed out. In the present study we show that intercellular transfers of functional P-gp occur by two different but complementary modalities through donor-recipient cells interactions in the absence of drug selection pressure. P-glycoprotein and drug efflux activity transfers were followed over 7 days by confocal microscopy and flow cytometry in drug-sensitive parental MCF-7 breast cancer cells co-cultured with P-gp overexpressing resistant variants. An early process of remote transfer was established based on the release and binding of P-gp-containing microparticles. Microparticle-mediated transfers were detected after only 4 h of incubation. We also identify an alternative mode of transfer by contact, consisting of cell-to-cell P-gp trafficking by tunneling nanotubes bridging neighboring cells. Our findings supply new mechanistic evidences for the extragenetic emergence of MDR in cancer cells and indicate that new treatment strategies designed to overcome MDR may include inhibition of both microparticles and Tunneling nanotube-mediated intercellular P-gp transfers.</p>
</abstract>
<kwd-group>
<kwd>ABC Transporter</kwd>
<kwd>Cancer</kwd>
<kwd>Drug Resistance</kwd>
<kwd>Flow Cytometry</kwd>
<kwd>Glycoprotein</kwd>
<kwd>MCF-7</kwd>
<kwd>Microparticles</kwd>
<kwd>P-glycoprotein</kwd>
<kwd>TnTs</kwd>
<kwd>Transfers</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>

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