Cigarette smoking induces overexpression of hepatocyte growth factor in type II pneumocytes and lung cancer cells.
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.
Chen
Jin-Tang
JT
Department of Health, Feng-Yuan Hospital, Taiwan.
Lin
Torng-Sen
TS
Chow
Kuan-Chih
KC
Huang
Hsuan-Hua
HH
Chiou
Shiow-Her
SH
Chiang
Shu-Fen
SF
Chen
Hong-Chen
HC
Chuang
Tzu-Lin
TL
Lin
Tze-Yi
TY
Chen
Chih-Yi
CY
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis*; D006801:Humans; D017403:In Situ Hybridization; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology*; D012907:Smoking / Q000009:adverse effects*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met