title: Differential signal transduction of epidermal-growth-factor receptors in hormone-dependent and hormone-independent human breast cancer cells.
abstract: 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.
authors.affiliation: Department of Research and Gynecology, University Clinics Medical School, Basel, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Mueller
authors.forename: P
authors.initials: P
authors.lastname: Loop
authors.forename: R
authors.initials: R
authors.lastname: Liu
authors.forename: K
authors.initials: K
authors.lastname: Wosikowski
authors.forename: W
authors.initials: W
authors.lastname: Kueng
authors.forename: U
authors.initials: U
authors.lastname: Eppenberger
mesh_terms: D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism*; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D016762:Genes, fos; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D014443:Tyrosine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D016650:Fluorescein-5-isothiocyanate