title: Role of FLT3 in the proliferation and aggressiveness of hepatocellular carcinoma.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey.
authors: Muammer Merve
authors: MM
authors: Aydin
authors: Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey.
authors: Nermin Sumru
authors: NS
authors: Bayin
authors: Department of Molecular Biology and Genetics, Faculty of Sciences and Arts, Bülent Ecevit University, Zonguldak, Turkey.
authors: Tolga
authors: T
authors: Acun
authors: Department of Molecular Biology and Genetics, Acıbadem University, İstanbul, Turkey.
authors: Mustafa Cengiz
authors: MC
authors: Yakicier
authors: Department of Biophysics, Ankara University, Faculty of Medicine, Ankara, Turkey.
authors: Kamil Can
authors: KC
authors: Akçali
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular; D049109:Cell Proliferation; D008113:Liver Neoplasms; D051379:Mice; D008819:Mice, Nude; D051941:fms-Like Tyrosine Kinase 3
chemical_list: C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3
keywords: Fms-like tyrosine kinase; invasiveness; liver cancer; regeneration; tyrosine kinase