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.

MATERIALS AND 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.

CONCLUSION:

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: Akira Kojima, Norio Horiguchi, Satoru Kakizaki, Hisashi Takayama, Masatomo Mori
• Journal: Anticancer research (Anticancer Res) Vol. 33 Issue 3 Pg. 895-901 (Mar 2013) ISSN: 1791-7530 [Electronic] Greece
• PMID: 23482759 (Publication Type: Journal Article)

Chemical References

• Diethylnitrosamine
• Hepatocyte Growth Factor
• Proto-Oncogene Proteins c-met

Topics

• Animals
• Diethylnitrosamine
• Female
• Hepatocyte Growth Factor (genetics, physiology)
• Lung Neoplasms (chemically induced)
• Male
• Mice
• Mice, Transgenic
• Proto-Oncogene Proteins c-met (analysis, physiology)