Evidence for a role of Met-HGF/SF during Ras-mediated tumorigenesis/metastasis.
Aberrations in Met-hepatocyte growth factor/scatter factor (HGF/SF) signaling have been implicated in the acquisition of tumorigenic and metastatic phenotypes. Here we show that murine NIH3T3 and C127 cells transformed by the Ras oncogene overexpress the Met receptor, resulting in enhanced HGF/SF-mediated responses in vitro including invasion through basement membrane. Accompanying the increase in Met in ras-transformed NIH3T3 cells, there is a decrease in endogenous HGF/SF expression as previously observed in cells exogenously overexpressing Met. However, subcutaneously grown tumors and experimental lung metastases derived from these cells express significantly higher levels of endogenous HGF/SF together with high levels of Met. These results suggest Met-HGF/SF signaling enhances tumor growth and metastasis of Ras-transformed NIH3T3 cells.
Webb
C P
CP
ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702, USA.
Taylor
G A
GA
Jeffers
M
M
Fiscella
M
M
Oskarsson
M
M
Resau
J H
JH
Vande Woude
G F
GF
D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D004285:Dogs; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D015689:Oncogene Protein p21(ras) / Q000235:genetics / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis / Q000502:physiology*
D019859:Proto-Oncogene Proteins c-met; D015689:Oncogene Protein p21(ras)