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      Role of FLT3 in the proliferation and aggressiveness of hepatocellular carcinoma

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      Author
      Aydın, Muammer Merve
      Bayın, Nermin Sumru
      Acun, T.
      Yakıcıer, M. C.
      Akçalı, K. C.
      Date
      2016
      Source Title
      Turkish Journal of Medical Sciences
      Print ISSN
      1300-0144
      Electronic ISSN
      1303-6165
      Publisher
      TÜBİTAK
      Volume
      46
      Issue
      2
      Pages
      572 - 581
      Language
      English
      Type
      Article
      Item Usage Stats
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      Abstract
      Background/aim: Previously we showed that Fms-like tyrosine kinase (FLT3) changes its cellular localization upon partial hepatectomy, suggesting a role in liver regeneration. FLT3 was also shown to play an important function in cellular proliferation and activation of PI3K and Ras. Thus, we aimed to investigate the role of FLT3 in hepatocellular tumorigenesis utilizing in vitro and in vivo models. Materials and methods: We used Snu398 cells that express FLT3. We investigated these cells in vitro proliferation and invasion abilities by treatment with the FLT3 inhibitor K-252a or by knocking-down with FLT3 shRNA,. Furthermore, the effect of blocking FLT3 activity and expression during in vivo tumorigenesis was assessed with xenograft models. Results: After K-252a treatment or stable knock-down, these cells proliferation and migration abilities were highly diminished in vitro. In addition, significant diminution in tumorigenicity of Snu398 cells was also obtained in vivo. When FLT3 knocked-down Snu398 cells were injected into nude mice, we did not detect αSMA expression in these tumors, suggesting a role for FLT3 in in vivo invasiveness. Conclusion: Our data provided evidence that FLT3 has a crucial role both in hepatocarcinogenesis and its invasiveness. Therefore, targeting FLT3 and/or its activity may be a promising tool for combating hepatocellular carcinomas.
      Keywords
      Fms-like tyrosine kinase
      Liver cancer
      Regeneration
      Invasiveness
      Tyrosine kinase
      Permalink
      http://hdl.handle.net/11693/54625
      Published Version (Please cite this version)
      https://doi.org/10.3906/sag-1501-173
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