Impaired response to hepatocyte growth factor in FRTL-5 rat thyroid cells expressing a functional hepatocyte growth factor receptor.
The FRTL-5 rat thyroid cell line is widely used for studies of thyrocyte function and growth. The objective of the present study was to investigate the effects of hepatocyte growth factor (HGF) on FRTL-5 cells. HGF has previously been known to be a potent regulator of thyrocyte growth and differentiation. Met, the receptor for HGF was expressed in FRTL-5 cells, as well as in primary cultures of porcine thyrocytes included in the study as control. On HGF stimulation Met was tyrosine phosphorylated in both porcine and FRTL-5 cells, indicating an activation of the receptor. Addition of HGF induced changes of cell shape, scattering and proliferation of the porcine thyrocytes, but not in the FRTL-5 cells; yet, a functional coupling of Met to the p85 subunit of the phosphatidylinositol-3'-kinase (PI3'-K) in coprecipitation experiments, formation of focal adhesions detected in immunofluorescence staining with an antivinculin antibody, and induction of c-fos mRNA in Northern blot analysis was observed in FRTL-5 cells, showing a transduction of the HGF/Met signal. In summary, despite the expression of apparently functional Met, the FRTL-5 cells are unable to properly respond to HGF.
Bergström
J D
JD
Department of Genetics and Pathology, Uppsala University Hospital, Sweden.
Nilsson
M
M
Heldin
N E
NE
D000818:Animals; D002478:Cells, Cultured; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D013552:Swine; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects*
D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met