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  • Svec, DavidGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Sahlgrenska Cancer Center,Institute of Biomedicine, Department of Pathology (author)

Identification of inhibitors regulating cell proliferation and FUS-DDIT3 expression in myxoid liposarcoma using combined DNA, mRNA, and protein analyses.

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • Elsevier BV,2018

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/266040
  • https://gup.ub.gu.se/publication/266040URI
  • https://doi.org/10.1038/s41374-018-0046-3DOI

Supplementary language notes

  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • FUS-DDIT3 belongs to the FET (FUS, EWSR1, and TAF15) family of fusion oncogenes, which collectively are considered to be key players in tumor development. Even though over 90% of all myxoid liposarcomas (MLS) have a FUS-DDIT3 gene fusion, there is limited understanding of the signaling pathways that regulate its expression. In order to study cell proliferation and FUS-DDIT3 regulation at mRNA and protein levels, we first developed a direct cell lysis approach that allows DNA, mRNA, and protein to be analyzed in the same sample using quantitative PCR, reverse transcription quantitative qPCR and proximity ligation assay, respectively. We screened 70 well-characterized kinase inhibitors and determined their effects on cell proliferation and expression of FUS-DDIT3 and FUS at both mRNA and protein levels in the MLS 402-91 cell line, where twelve selected inhibitors were evaluated further in two additional MLS cell lines. Both FUS-DDIT3 and FUS mRNA expression correlated with cell proliferation and both transcripts were co-regulated in most conditions, indicating that the common 5' FUS promotor is important in transcriptional regulation. In contrast, FUS-DDIT3 and FUS protein levels displayed more cell line dependent expression. Furthermore, most JAK inhibitors caused FUS-DDIT3 downregulation at both mRNA and protein levels. In conclusion, defining factors that regulate FUS-DDIT3 expression opens new means to understand MLS development at the molecular level.

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  • Dolatabadi, SoheilaGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Sahlgrenska Cancer Center,Institute of Biomedicine, Department of Pathology(Swepub:gu)xdolso (author)
  • Thomsen, Christer,1977Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology(Swepub:gu)xtchrb (author)
  • Cordes, NicoleGothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology (author)
  • Shannon, Mark (author)
  • Fitzpatrick, Paul A.Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Sahlgrenska Cancer Center,Institute of Biomedicine, Department of Pathology(Swepub:gu)xfitpa (author)
  • Landberg, Göran,1963Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Sahlgrenska Cancer Center,Institute of Biomedicine, Department of Pathology(Swepub:gu)xlgora (author)
  • Åman, Pierre,1953Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology(Swepub:gu)xamapi (author)
  • Ståhlberg, Anders,1975Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology(Swepub:gu)xsandw (author)
  • Göteborgs universitetInstitutionen för biomedicin, avdelningen för patologi (creator_code:org_t)

Related titles

  • In:Laboratory investigation; a journal of technical methods and pathology: Elsevier BV98, s. 957-9671530-0307
  • In:Laboratory Investigation: Elsevier BV98, s. 957-9670023-6837

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