title: Insulin activates EGFR by stimulating its interaction with IGF-1R in low-EGFR-expressing TNBC cells.
abstract: The expression of epidermal growth factor receptor (EGFR) is an important diagnostic marker for triple-negative breast cancer (TNBC) cells, which lack three hormonal receptors: estrogen and progesterone receptors as well as epidermal growth factor receptor 2. EGFR transactivation can cause drug resistance in many cancers including TNBC, but the mechanism underlying this phenomenon is poorly defined. Here, we demonstrate that insulin treatment induces EGFR activation by stimulating the interaction of EGFR with insulin-like growth factor receptor 1 (IGF-1R) in the MDA-MB-436 TNBC cell line. These cells express low levels of EGFR, while exhibiting high levels of IGF-1R expression and phosphorylation. Low-EGFRexpressing MDA-MB-436 cells show high sensitivity to insulinstimulated cell growth. Therefore, unexpectedly, insulin stimulation induced EGFR transactivation by regulating its interaction with IGF-1R in low-EGFR-expressing TNBC cells.
authors.affiliation: Division of Life Sciences, Korea University, Seoul 136-701; Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Korea.
authors.forename: Miyoung
authors.initials: M
authors.lastname: Shin
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Korea.
authors.forename: Eun Gyeong
authors.initials: EG
authors.lastname: Yang
authors.affiliation: Division of Life Sciences, Korea University, Seoul 136-701, Korea.
authors.forename: Hyun Kyu
authors.initials: HK
authors.lastname: Song
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Korea; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
authors.forename: Hyesung
authors.initials: H
authors.lastname: Jeon
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D007328:Insulin; C512478:EGFR protein, human; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1