Cigarette smoking induces overexpression of hepatocyte growth factor in type II pneumocytes and lung cancer cells

Am J Respir Cell Mol Biol. 2006 Mar;34(3):264-73. doi: 10.1165/rcmb.2005-0117OC. Epub 2005 Oct 27.


We examined gene expression of hepatocyte growth factor (HGF) and HGF receptor (HGFR), or product of proto-oncogene c-met (c-met), in smokers and nonsmokers with adenocarcinoma (ADC) by suppression subtractive hybridization and microarray techniques. Expression of HGF and c-met was confirmed by RT-PCR. HGF content in the respective tumor mass and nontumor lung tissue was measured by ELISA. HGF in pathologic samples was localized by immunohistochemistry and in situ hybridization. Our results indicate that overexpression of HGFR was frequently detected in ADC cells, whereas overexpression of HGF was detected in alveolar type II (ATII) cells. Overexpression of HGF was correlated with cigarette smoking and tumor stages. In vitro, HGF expression was evaluated in isolated murine ATII cells and in 12 ADC cell lines, and we found that nicotine activated HGF expression in ATII cells and lung cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Animals
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Gene Expression Regulation, Neoplastic
  • Hepatocyte Growth Factor / biosynthesis*
  • Humans
  • In Situ Hybridization
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Proto-Oncogene Proteins c-met / metabolism
  • Pulmonary Alveoli / metabolism
  • Pulmonary Alveoli / pathology*
  • Smoking / adverse effects*


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