High expression of Met/hepatocyte growth factor receptor suppresses tumorigenicity in NCI-H1264 lung carcinoma cells.
The protein product of c-met proto-oncogene, Met, is a tyrosine kinase receptor for the hepatocyte growth factor (HGF). Met receptor is expressed in normal human bronchial epithelium. In comparison, its expression in squamous cell carcinoma (SQCC) of the lung is markedly decreased in a great majority of cases. To understand further the role of Met receptor overexpression in non-small-cell lung carcinoma, we forced-expressed the full-length met cDNA in the NCI-H1264 (H1264) lung carcinoma cell line with low constitutive expression of this receptor. In vitro studies demonstrated that increased Met expression in H1264 cells resulted in strong inhibition of their ability to form soft agar colonies and in marked suppression of tumorigenicity in the subcutaneous tissue of immune-deficient mice. This is despite inconsistent alteration in the proliferation rate on plastic surfaces. Tumor cells explanted from occasional xenograft tumors formed by the Met-overexpressing H1264 cells also demonstrated marked down-regulation of the receptor protein levels as compared to the transplanted cells. The results suggest that constitutive overexpression of Met receptor may negatively regulate the malignancy of certain human lung cancer cells.
To
Christine
C
University Health Network-Ontario Cancer Institute/Princess Margaret Hospital, University of Toronto, Ontario, Toronto, M5G 2M9, Canada.
Seiden
Isolde
I
Liu
Ni
N
Wigle
Dennis
D
Tsao
Ming-Sound
MS
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D015197:Carcinogenicity Tests; D018196:Carcinoma, Adenosquamous / Q000378:metabolism* / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D002455:Cell Division; D017931:DNA Primers / Q000737:chemistry; D016228:Endothelial Growth Factors / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D017931:DNA Primers; D016228:Endothelial Growth Factors; D008222:Lymphokines; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met