bFGF and aFGF induce membrane ruffling in breast cancer cells but not in normal breast epithelial cells: FGFR-4 involvement.
Acidic and basic fibroblast growth factors (aFGF and bFGF) are growth factors which may have a physiological role in the normal breast and in breast cancer. A study of the effects of aFGF and bFGF on a variety of breast cell lines and epithelial cells purified from normal breast organoids showed that whereas normal breast cells did not exhibit membrane ruffling in response to either of these growth factors, some breast cancer cell lines did. This difference was not due to lack of receptor since all the cell lines tested were mitogenically stimulated by bFGF. Dominant negative mutations of FGF receptor 3 (FGFR-3) and the small GTP-binding protein p21rac inhibited membrane ruffling, showing that receptor dimerization and phosphorylation and p21rac activation are prerequisites for membrane ruffling in response to aFGF and bFGF. Transient transfection of individual FGFRs into cos-7 cells showed that FGFR-1, FGFR-2 and FGFR-3 could not mediate a membrane ruffling response whereas FGFR-4 could. These studies elucidate one signalling mechanism of FGF and point to differences in the response of normal and cancer breast epithelial cells which may be important in cell motility.
Johnston
C L
CL
Department of Medical Oncology, Charing Cross and Westminster Medical School, London, U.K.
Cox
H C
HC
Gomm
J J
JJ
Coombes
R C
RC
D016475:3T3 Cells / Q000648:ultrastructure; D000818:Animals; D001940:Breast / Q000648:ultrastructure*; D001943:Breast Neoplasms / Q000648:ultrastructure*; D002462:Cell Membrane / Q000473:pathology*; D004848:Epithelium / Q000648:ultrastructure; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D016297:Mutagenesis, Site-Directed; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3; D051499:Receptor, Fibroblast Growth Factor, Type 4; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D020744:rac GTP-Binding Proteins
D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; C496365:FGFR3 protein, human; C496371:FGFR4 protein, human; C496366:Fgfr3 protein, mouse; C496372:Fgfr4 protein, mouse; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3; D051499:Receptor, Fibroblast Growth Factor, Type 4; D019204:GTP-Binding Proteins; D020744:rac GTP-Binding Proteins