THE LOCATION OF ACIDIC FIBROBLAST GROWTH-FACTOR IN THE BREAST IS DEPENDENT ON THE ACTIVITY OF PROTEASES PRESENT IN BREAST-CANCER TISSUE

Acidic fibroblast growth factor (FGF1) and two of its receptors, FGFR1 and FGFR4, were localized in cryostat sections of normal, benign and malignant human breast tissue by immunohistochemistry. Without pretrea tment, FGF1 staining was mainly seen in normal epithelial cells. Howev er, polymerase chain reaction (PCR) analysis and immunoblotting of iso lated normal epithelial and myoepithelial cells showed FGF1 mRNA and p rotein to be present in both cell types. Following incubation of froze n sections at 37 degrees C in phosphate-buffered saline, FGF1 staining was also revealed in myoepithelial cells and basement membrane adjace nt to carcinoma cells. Treatment with protease inhibitors demonstrated that this effect was due to the activity of an endogenous protease. I n contrast, FGF1 staining was found to be associated with the stroma a djacent to malignant cells only in the presence of protease inhibitors . FGFR1 and FGFR4 immunostaining was localized to both normal and mali gnant epithelial cells and to a lesser extent to myoepithelial cells. There was no difference in the staining intensity for the FGF receptor s between normal and cancer samples. The change in location of FGF1 be tween normal and malignant tissues and the sensitivity of stored FGF1 to the action of endogenous proteases raises the possibility of both a utocrine and paracrine roles for FGF1 in the normal and malignant huma n breast.