title: Hepatocyte growth factor promotes lung carcinogenesis in transgenic mice treated with diethylnitrosamine.
abstract: BACKGROUND
  Hepatocyte growth factor (HGF) was initially discovered as a mitogen for hepatocytes, but it is also known to be related to carcinogenesis in many other organs. However, the role of HGF in lung carcinogenesis is not fully-understood. In this study, we investigated the role of HGF in lung carcinogenesis using HGF transgenic mice.
  
  
  METHODS
  To elucidate the role of HGF in lung carcinogenesis, 5 μg/g body weight diethylnitrosamine (DEN) were administered intraperitoneally to HGF transgenic (TG) mice and wild-type (WT) mice at 15 days of age. The incidence and number of lung tumors, the expression of HGF and of its receptor (c-Met) were compared between HGF TG and WT mice.
  
  
  RESULTS
  HGF overexpression accelerated DEN-induced lung carcinogenesis. Seventy-six percent of TG mice (versus 50% of WT mice) developed malignant lung tumors by 48 weeks. The incidence of lung tumors was significantly higher in the TG mice in comparison with WT mice (p<0.05). Furthermore, the mean diameter and number of tumors in each mouse were significantly higher in the TG mice compared to the WT mice (p<0.01). The northern blotting analyses revealed that there was overexpression of the HGF transgene in the lung tumors of TG mice in comparison with the surrounding non-tumorous lesions. The western blotting analyses of the tumor lesions revealed increased phosphorylation of c-Met.
  
  
  CONCLUSIONS
  Our results suggest that HGF promotes lung carcinogenesis through the autocrine activation of the HGF/c-Met signaling pathway. The HGF/c-Met signaling pathway appears to have vital roles in lung carcinogenesis.
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi Maebashi, Gunma 371-8511, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kojima
authors.forename: Norio
authors.initials: N
authors.lastname: Horiguchi
authors.forename: Satoru
authors.initials: S
authors.lastname: Kakizaki
authors.forename: Hisashi
authors.initials: H
authors.lastname: Takayama
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
mesh_terms: D000818:Animals; D004052:Diethylnitrosamine; D005260:Female; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000502:physiology*; D008175:Lung Neoplasms / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis / Q000502:physiology
chemical_list: D004052:Diethylnitrosamine; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met