LymphedemaV1, Pmc, Curation, bibRecord, 001752

Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1 homeobox transcription factor

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Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1 homeobox transcription factor

Auteurs : Tatiana V. Petrova ; Taija M Kinen ; Tomi P. M Kel ; Janna Saarela ; Ismo Virtanen ; Robert E. Ferrell ; David N. Finegold ; Dontscho Kerjaschki ; Seppo Yl Herttuala ; Kari Alitalo

Source :

The EMBO Journal [ 0261-4189 ] ; 2002.

RBID : PMC:125413

Abstract

Lymphatic vessels are essential for fluid homeostasis, immune surveillance and fat adsorption, and also serve as a major route for tumor metastasis in many types of cancer. We found that isolated human primary lymphatic and blood vascular endothelial cells (LECs and BECs, respectively) show interesting differences in gene expression relevant for their distinct functions in vivo. Although these phenotypes are stable in vitro and in vivo, overexpression of the homeobox transcription factor Prox-1 in the BECs was capable of inducing LEC-specific gene transcription in the BECs, and, surprisingly, Prox-1 suppressed the expression of ∼40% of the BEC-specific genes. Prox-1 did not have global effects on the expression of LEC-specific genes in other cell types, except that it up-regulated cyclin E1 and E2 mRNAs and activated the cyclin e promoter in various cell types. These data suggest that Prox-1 acts as a cell proliferation inducer and a fate determination factor for the LECs. Furthermore, the data provide insights into the phenotypic diversity of endothelial cells and into the possibility of transcriptional reprogramming of differentiated endothelial cells.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC125413

DOI: 10.1093/emboj/cdf470
PubMed: 12198161
PubMed Central: 125413

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PMC:125413

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<author><name sortKey="Petrova, Tatiana V" sort="Petrova, Tatiana V" uniqKey="Petrova T" first="Tatiana V." last="Petrova">Tatiana V. Petrova</name>
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<author><name sortKey="M Kinen, Taija" sort="M Kinen, Taija" uniqKey="M Kinen T" first="Taija" last="M Kinen">Taija M Kinen</name>
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<front><div type="abstract" xml:lang="en"><p>Lymphatic vessels are essential for fluid homeostasis, immune surveillance and fat adsorption, and also serve as a major route for tumor metastasis in many types of cancer. We found that isolated human primary lymphatic and blood vascular endothelial cells (LECs and BECs, respectively) show interesting differences in gene expression relevant for their distinct functions <italic>in vivo</italic>
. Although these phenotypes are stable <italic>in vitro</italic>
 and <italic>in vivo</italic>
, overexpression of the homeobox transcription factor Prox-1 in the BECs was capable of inducing LEC-specific gene transcription in the BECs, and, surprisingly, Prox-1 suppressed the expression of ∼40% of the BEC-specific genes. Prox-1 did not have global effects on the expression of LEC-specific genes in other cell types, except that it up-regulated cyclin E1 and E2 mRNAs and activated the <italic>cyclin e</italic>
 promoter in various cell types. These data suggest that Prox-1 acts as a cell proliferation inducer and a fate determination factor for the LECs. Furthermore, the data provide insights into the phenotypic diversity of endothelial cells and into the possibility of transcriptional reprogramming of differentiated endothelial cells.</p>
</div>
</front>
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<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">EMBO J</journal-id>
<journal-title>The EMBO Journal</journal-title>
<issn pub-type="ppub">0261-4189</issn>
<issn pub-type="epub">1460-2075</issn>
<publisher><publisher-name>Oxford University Press</publisher-name>
<publisher-loc>Oxford, UK</publisher-loc>
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<article-meta><article-id pub-id-type="pmid">12198161</article-id>
<article-id pub-id-type="pmc">125413</article-id>
<article-id pub-id-type="publisher-id">cdf470</article-id>
<article-id pub-id-type="doi">10.1093/emboj/cdf470</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
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</article-categories>
<title-group><article-title>Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1 homeobox transcription factor</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Petrova</surname>
<given-names>Tatiana V.</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Mäkinen</surname>
<given-names>Taija</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Mäkelä</surname>
<given-names>Tomi P.</given-names>
</name>
<xref ref-type="aff" rid="N0x9921fd8.0x98aa4f8">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Saarela</surname>
<given-names>Janna</given-names>
</name>
<xref ref-type="aff" rid="N0x9921fd8.0x98aa4f8">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Virtanen</surname>
<given-names>Ismo</given-names>
</name>
<xref ref-type="aff" rid="N0x9921fd8.0x98aa4f8">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ferrell</surname>
<given-names>Robert E.</given-names>
</name>
<xref ref-type="aff" rid="N0x9921fd8.0x98aa4f8">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Finegold</surname>
<given-names>David N.</given-names>
</name>
<xref ref-type="aff" rid="N0x9921fd8.0x98aa4f8">4</xref>
<xref ref-type="aff" rid="N0x9921fd8.0x98aa4f8">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kerjaschki</surname>
<given-names>Dontscho</given-names>
</name>
<xref ref-type="aff" rid="N0x9921fd8.0x98aa4f8">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ylä-Herttuala</surname>
<given-names>Seppo</given-names>
</name>
<xref ref-type="aff" rid="N0x9921fd8.0x98aa4f8">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Alitalo</surname>
<given-names>Kari</given-names>
</name>
<xref ref-type="aff" rid="N0x9921fd8.0x98aa4f8">8</xref>
</contrib>
</contrib-group>
<aff id="N0x9921fd8.0x98aa4f8">Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Haartman Institute and Helsinki University Central Hospital,<label>1</label>
Cell Cycle Laboratory,<label>2</label>
National Public Health Institute and<label>3</label>
Department of Anatomy, Biomedicum Helsinki, University of Helsinki, 00014 Helsinki,<label>4</label>
Department of Human Genetics and<label>5</label>
Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA,<label>6</label>
Department of Pathology, University of Vienna Medical School, 1090 Vienna, Austria and<label>7</label>
Department of Molecular Medicine, A.I. Virtanen Institute, University of Kuopio, 70211 Kuopio, Finland<label>8</label>
Corresponding author e-mail: Kari.Alitalo@Helsinki.FI T.V.Petrova and T.Mäkinen contributed equally to this work</aff>
<pub-date pub-type="ppub"><day>2</day>
<month>9</month>
<year>2002</year>
</pub-date>
<volume>21</volume>
<issue>17</issue>
<fpage>4593</fpage>
<lpage>4599</lpage>
<ext-link ext-link-type="uri" xlink:href="http://www.emboj.oupjournals.org/content/vol21/issue17/"></ext-link>
<history><date date-type="received"><day>17</day>
<month>6</month>
<year>2002</year>
</date>
<date date-type="rev-recd"><day>17</day>
<month>7</month>
<year>2002</year>
</date>
<date date-type="accepted"><day>17</day>
<month>7</month>
<year>2002</year>
</date>
</history>
<copyright-statement>Copyright © 2002 European Molecular Biology Organization</copyright-statement>
<copyright-year>2002</copyright-year>
<abstract><p>Lymphatic vessels are essential for fluid homeostasis, immune surveillance and fat adsorption, and also serve as a major route for tumor metastasis in many types of cancer. We found that isolated human primary lymphatic and blood vascular endothelial cells (LECs and BECs, respectively) show interesting differences in gene expression relevant for their distinct functions <italic>in vivo</italic>
. Although these phenotypes are stable <italic>in vitro</italic>
 and <italic>in vivo</italic>
, overexpression of the homeobox transcription factor Prox-1 in the BECs was capable of inducing LEC-specific gene transcription in the BECs, and, surprisingly, Prox-1 suppressed the expression of ∼40% of the BEC-specific genes. Prox-1 did not have global effects on the expression of LEC-specific genes in other cell types, except that it up-regulated cyclin E1 and E2 mRNAs and activated the <italic>cyclin e</italic>
 promoter in various cell types. These data suggest that Prox-1 acts as a cell proliferation inducer and a fate determination factor for the LECs. Furthermore, the data provide insights into the phenotypic diversity of endothelial cells and into the possibility of transcriptional reprogramming of differentiated endothelial cells.</p>
</abstract>
<kwd-group><kwd>gene profiling/lymphatic endothelium/transcription factor Prox-1</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>

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Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1 homeobox transcription factor

Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1 homeobox transcription factor

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Abstract

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