<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>Blum, Walter</dc:creator>
  <dc:creator>Schwaller, Beat</dc:creator>
  <dc:date>2013</dc:date>
  <dc:description xmlns:ns0="xml" ns0:lang="en">Malignant mesothelioma (MM) are highly aggressive asbestos-related neoplasms, which show strong chemotherapy-resistance and there is no effective cure for MM so far. Calretinin (CR) is widely used as a diagnostic marker for epithelioid and mixed (biphasic) mesothelioma, but still little is known about CR's putative function(s) in tumorigenesis. CR protects against asbestos-induced acute cytotoxicity mediated by the AKT/PI3K pathway and furthermore, SV40 early region genes are able to up-regulate CR in mesothelial cells. However, the precise role of CR in mesothelioma is still unknown. Down-regulation of CR via lentiviral-mediated shRNA significantly decreased the viability and proliferation of mesothelioma cells &lt;em&gt;in vitro&lt;/em&gt;. The effect was strong in epithelioid-dominated cell lines (ZL55, MSTO-211H). A weaker and delayed effect was observed in mesothelioma cells with prevalent sarcomatoid morphology (SPC111, SPC212, ZL34). The specificity of the effect was confirmed by stable eGFP-CR expression in mesothelioma cell lines and subsequent down-regulation. Depletion of CR led these cancer cell lines to enter apoptosis within 72h post-infection via strong activation of the intrinsic caspase 9-dependent pathway. Down-regulation of CR in immortalized mesothelial cells LP9/TERT-1 strongly blocked proliferation and caused a G₁ block without decreasing viability or activating apoptosis pathways. Our results demonstrate that down-regulation of CR had a strong effect on the viability of MM cells and that CR is essential for cells derived from malignant mesothelioma. We anticipate these findings to reveal calretinin as a highly interesting new putative therapeutic target for mesothelioma treatment of especially the epithelioid, but also of the mixed and sarcomatoid type.</dc:description>
  <dc:format>application/pdf</dc:format>
  <dc:identifier>https://folia.unifr.ch/global/documents/303021</dc:identifier>
  <dc:identifier>https://folia.unifr.ch/documents/303021/files/sch_cem.pdf</dc:identifier>
  <dc:language>eng</dc:language>
  <dc:relation>info:eu-repo/semantics/altIdentifier/doi/10.1002/ijc.28218</dc:relation>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>License undefined</dc:rights>
  <dc:source>International Journal of Cancer. - 2013, p. –</dc:source>
  <dc:subject>info:eu-repo/classification/udc/57</dc:subject>
  <dc:title xmlns:ns1="xml" ns1:lang="en">Calretinin is essential for mesothelioma cell growth/survival in vitro: A potential new target for malignant mesothelioma therapy?</dc:title>
  <dc:type>http://purl.org/coar/resource_type/c_6501</dc:type>
</oai_dc:dc>