EXPRESSION OF KERATINOCYTE GROWTH-FACTOR AND ITS RECEPTOR IN HUMAN BREAST-CANCER

The level of expression of keratinocyte growth factor (KGF) mRNA has b een measured in human breast cell lines, purified populations of epith elial cells, myoepithelial cells and fibroblasts from reduction mammop lasty tissue and a panel of 42 breast cancers and 30 non-malignant hum an breast tissues using a semiquantitative reverse transcriptase polym erase chain reaction (RT-PCR) procedure. We found similar levels of KG F mRNA in malignant and non-malignant breast tissues. The study of the amount of KGF mRNA in breast cell lines and purified populations of c ells revealed that fibroblasts are the predominant source of KGF with malignant and non-malignant epithelial cells containing Very low level s of KGF mRNA. We have examined the distribution of fibroblast growth factor receptor (FGFR)-2-IIIb, which is a high-affinity receptor for K GF and find that it is present on malignant and non-malignant epitheli al cells. The level of FGFR-2-IIIb present on breast cancer cell lines was sufficient for KGF stimulation of breast cancer cell proliferatio n. Other members of the fibroblast growth factor family have been eith er not expressed in the human breast (FGF3, FGF4) or have been found a t much reduced levels in breast cancer (FGF1, FGF2) and this is the fi rst member of the family to potentially influence the progression of b reast cancer through stimulation of cell division.