<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Walpen T</dc:creator>
  <dc:creator>Peier M</dc:creator>
  <dc:creator>Haas E</dc:creator>
  <dc:creator>Kalus I</dc:creator>
  <dc:creator>Schwaller J</dc:creator>
  <dc:creator>Battegay E</dc:creator>
  <dc:creator>Humar R</dc:creator>
  <dc:date>2012</dc:date>
  <dc:description xmlns:ns0="xml" ns0:lang="en">BACKGROUND
PIM1 is a constitutively active serine-threonine kinase regulating cell survival and proliferation. Increased PIM1 expression has been correlated with cancer metastasis by facilitating migration and anti-adhesion. Endothelial cells play a pivotal role in these processes by contributing a barrier to the blood stream. Here, we investigated whether PIM1 regulates mouse aortic endothelial cell (MAEC) monolayer integrity.


METHODS
Pim1-/-MAEC were isolated from Pim1 knockout mice and used in trypsinization-, wound closure assays, electrical cell-substrate sensing, immunostaining, cDNA transfection and as RNA source for microarray analysis.


RESULTS
Pim1-/-MAEC displayed decreased migration, slowed cell detachment and increased electrical resistance across the endothelial monolayer. Reintroduction of Pim1- cDNA into Pim1-/-MAEC significantly restored wildtype adhesive characteristics. Pim1-/--MAEC displayed enhanced focal adhesion and adherens junction structures containing vinculin and β-catenin, respectively. Junctional molecules such as Cadherin 13 and matrix components such as Collagen 6a3 were highly upregulated in Pim1-/- cells. Intriguingly, extracellular matrix deposited by Pim1-/- cells alone was sufficient to induce the hyperadhesive phenotype in wildtype endothelial cells.


CONCLUSION
Loss of Pim1 induces a strong adhesive phenotype by enhancing endothelial cell-cell and cell-matrix adhesion by the deposition of a specific extracellular matrix. Targeting PIM1 function therefore might be important to promote endothelial barrier integrity.</dc:description>
  <dc:format>application/pdf</dc:format>
  <dc:identifier>https://sonar.ch/global/documents/81082</dc:identifier>
  <dc:language>eng</dc:language>
  <dc:relation>info:eu-repo/semantics/altIdentifier/doi/10.1159/000341484</dc:relation>
  <dc:relation>info:eu-repo/semantics/altIdentifier/pmid/23202547</dc:relation>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:source>Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. - 2012</dc:source>
  <dc:subject xmlns:ns1="xml" ns1:lang="en">Adherens Junctions</dc:subject>
  <dc:subject xmlns:ns2="xml" ns2:lang="en">Animals</dc:subject>
  <dc:subject xmlns:ns3="xml" ns3:lang="en">Aorta</dc:subject>
  <dc:subject xmlns:ns4="xml" ns4:lang="en">Cell Adhesion</dc:subject>
  <dc:subject xmlns:ns5="xml" ns5:lang="en">Cell Movement</dc:subject>
  <dc:subject xmlns:ns6="xml" ns6:lang="en">Cells, Cultured</dc:subject>
  <dc:subject xmlns:ns7="xml" ns7:lang="en">Endothelial Cells</dc:subject>
  <dc:subject xmlns:ns8="xml" ns8:lang="en">Focal Adhesions</dc:subject>
  <dc:subject xmlns:ns9="xml" ns9:lang="en">Gene Deletion</dc:subject>
  <dc:subject xmlns:ns10="xml" ns10:lang="en">Humans</dc:subject>
  <dc:subject xmlns:ns11="xml" ns11:lang="en">Mice</dc:subject>
  <dc:subject xmlns:ns12="xml" ns12:lang="en">Mice, Knockout</dc:subject>
  <dc:subject xmlns:ns13="xml" ns13:lang="en">Proto-Oncogene Proteins c-pim-1</dc:subject>
  <dc:subject xmlns:ns14="xml" ns14:lang="en">Transfection</dc:subject>
  <dc:subject xmlns:ns15="xml" ns15:lang="en">Wound Healing</dc:subject>
  <dc:title xmlns:ns16="xml" ns16:lang="en">Loss of pim1 imposes a hyperadhesive phenotype on endothelial cells.</dc:title>
  <dc:type>http://purl.org/coar/resource_type/c_6501</dc:type>
</oai_dc:dc>