Induction of c-met proto-oncogene expression at the metastatic site.
In metastatic processes, gene expression may variously alter through interactions between tumor and host stromal cells at the metastatic site. Using a tail vein injection-lung metastatic model and differential display, we analyzed alteration of gene expression in experimentally metastasized lesions. We found that expression of the c-met proto-oncogene was elevated in the lungs metastasized by MC-1 cells. The up-regulation of c-met was also observed in the lungs metastasized by B16 melanoma cells. In situ hybridization analysis revealed that the elevation of c-met expression apparently occurred in tumor cells but did not in lung stromal cells at the metastatic site. The c-Met protein was also highly expressed and phosphorylated. The upregulation of c-met appeared to be caused by induction of gene expression but not to be due to preferential selection of tumor cells highly expressing c-met. These findings suggest that the c-met proto-oncogene is up-regulated at the transcription level through some interactions between tumor and host stromal cells.
Imai
J
J
Department of Virology, The Institute of Medical Science, The University of Tokyo, Japan.
Watanabe
M
M
Sasaki
M
M
Yamaguchi
R
R
Tateyama
S
S
Sugano
S
S
D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000235:genetics; D009368:Neoplasm Transplantation; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis / Q000235:genetics*; D014407:Tumor Cells, Cultured
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met