BFGF AND AFGF INDUCE MEMBRANE RUFFLING IN BREAST-CANCER CELLS BUT NOTIN 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 i n 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 memb rane ruffling in response to either of these growth factors, some brea st cancer cell lines did. This difference was not due to lack of recep tor since all the cell lines tested were mitogenically stimulated by b FGF. Dominant negative mutations of FGF receptor 3 (FGFR-3) and the sm all GTP-binding protein p21rac inhibited membrane ruffling, showing th at receptor dimerization and phosphorylation and p2lrac activation are prerequisites for membrane ruffling in response to aFGF and bFGF. Tra nsient transfection of individual FGFRs into cos-7 cells showed that F GFR-1, FGFR-2 and FGFR-3 could not mediate a membrane ruffling respons e whereas FGFR-4 could. These studies elucidate one signalling mechani sm of FGF and point to differences in the response of normal and cance r breast epithelial cells which may be important in cell motility.