title: Expression of Rab5a in hepatocellular carcinoma: Possible involvement in epidermal growth factor signaling.
abstract: OBJECTIVE
  The Rab subfamily plays a role in intracellular transport. Rab5a is, in particular, involved in receptor-mediated endocytosis. Epidermal growth factor (EGF) is known to induce cell migration and promote invasion and angiogenesis. The EGF receptor (EGFR) is actively internalized upon the addition of EGF. The aim of the present study was to clarify the expression of Rab5a in hepatocellular carcinomas (HCC) and to examine its effect on EGF signaling.
  
  
  METHODS
  The expression of the Rab5a protein in HCC and corresponding non-tumorous tissues from 23 patients with HCC who had undergone surgical resection were analyzed by immunoblotting. A stable transfectant of Rab5a dominant negative (S34N) was established in a human hepatoma cell line, PLC/PRF/5 (PLC/PRF/5/Rab5aDN).
  
  
  RESULTS
  High expression (tumor/non-tumor (T/N) ratios >/= 1) of Rab5a protein in HCC compared to the paired non-tumortissues was recognized in 15 patients (65.2%) of 23 samples. The Rab5a antigen was diffusely expressed in the cytoplasm and membranes of the cancer cells. The membrane-associated Rab5a is also enhanced via overexpression in HCC. The EGF-induced endocytosis of EGFR and the phosphorylation of MAP kinase were inhibited in PLC/PRF/5/Rab5aDN cells. The migration of PLC/PRF/5/Rab5aDN cells induced by EGF was also significantly attenuated.
  
  
  CONCLUSIONS
  These results indicate that the overexpression of Rab5a in HCC may play an important role in EGF signaling.
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, Osaka, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Fukui
authors.forename: Shinji
authors.initials: S
authors.lastname: Tamura
authors.forename: Akira
authors.initials: A
authors.lastname: Wada
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kamada
authors.forename: Takumi
authors.initials: T
authors.lastname: Igura
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kiso
authors.forename: Norio
authors.initials: N
authors.lastname: Hayashi