DIFFERENTIAL SIGNAL-TRANSDUCTION OF EPIDERMAL-GROWTH-FACTOR RECEPTORSIN HORMONE-DEPENDENT AND HORMONE-INDEPENDENT HUMAN BREAST-CANCER CELLS

In breast cancer, hormone dependency is inversely correlated with the number of surface epidermal-growth-factor (EGF) receptors on the tumor cells. In vitro, EGF stimulated only hormone-dependent immortalized h uman breast cancer cells to grow with an increased rate whereas hormon e-independent cells were not affected by EGF. The number of EGF surfac e receptors is about 5-10-times smaller on hormone-dependent cells tha n on hormone-independent cells. Two cell lines representing the two ce ll types were used to demonstrate the signal-transduction capabilities of the EGF receptors. The two cell lines were the hormone-dependent M CF-7 cells and the hormone-independent MDA-MB-231 cells. Incubation at 37 degrees C for 15 min with 10(-8) M EGF increased the surface EGF-r eceptor density substantially on MCF-7 cells (50%) and reduced the num ber of these receptors on MDA-MB-231 cells to about 65% of the control . Both cell lines internalized a fluoresceinisothiocyanate-labeled EGF with similar kinetics. EGF triggered tyrosine phosphorylation of seve ral targets in isolated MCF-7 cell membranes. One of these targets was shown by immunoprecipitation to be the EGF receptor. In MDA-MB-231 ce ll membranes, the EGF receptor was demonstrated to be the main target for tyrosine phosphorylation. The mRNA expression of the immediate ear ly proto-oncogene c-fos was stimulated by EGF only in MCF-7 cells. In contrast, the mRNA of the EGF receptors was stimulated by EGF in both cell lines. These results demonstrate that, although EGF-binding sites are present on both cell lines, their signal-transduction capacity an d activities are substantially different and resulted in a divergent r esponse of the two cell types to EGF.