Differential signal transduction of epidermal-growth-factor receptors in 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 human breast cancer cells to grow with an increased rate whereas hormone-independent cells were not affected by EGF. The number of EGF surface receptors is about 5-10-times smaller on hormone-dependent cells than on hormone-independent cells. Two cell lines representing the two cell types were used to demonstrate the signal-transduction capabilities of the EGF receptors. The two cell lines were the hormone-dependent MCF-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-receptor density substantially on MCF-7 cells (50%) and reduced the number of these receptors on MDA-MB-231 cells to about 65% of the control. Both cell lines internalized a fluorescein-isothiocyanate-labeled EGF with similar kinetics. EGF triggered tyrosine phosphorylation of several targets in isolated MCF-7 cell membranes. One of these targets was shown by immunoprecipitation to be the EGF receptor. In MDA-MB-231 cell membranes, the EGF receptor was demonstrated to be the main target for tyrosine phosphorylation. The mRNA expression of the immediate early 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 and activities are substantially different and resulted in a divergent response of the two cell types to EGF.