title: EGFR Activation Leads to Cell Death Independent of PI3K/AKT/mTOR in an AD293 Cell Line.
abstract: The Epidermal Growth Factor Receptor (EGFR) and its mutations contribute in various ways to tumorigenesis and biology of human cancers. They are associated with tumor proliferation, progression, drug resistance and the process of apoptosis. There are also reports that overexpression and activation of wild-type EGFR may lead to cell apoptosis. To study this phenomenon, we overexpressed in an AD293 cell line two most frequently observed forms of the EGFR receptor: wild-type and the constitutively active mutant-EGFR variant III (EGFRvIII). Then, we compared the effect of EGF stimulation on cell viability and downstream EGFR signaling. AD293 cells overexpressing wild-type EGFR, despite a significant proliferation increase in serum supplemented medium, underwent apoptosis after EGF stimulation in serum free conditions. EGFRvIII expressing cells, however, were unaffected by either serum starvation or EGF treatment. The effect of EGF was completely neutralized by tyrosine kinase inhibitors (TKIs), indicating the specificity of this observation. Moreover, apoptosis was not prevented by inhibiting EGFR downstream proteins (PI3K, AKT and mTOR). Here we showed another EGFR function, dependent on environmental factors, which could be employed in therapy and drug design. We also proposed a new tool for EGFR inhibitor analysis.
authors.affiliation: Department of Research and Development, Celther Polska Ltd., Lodz, Poland.
authors.forename: Cezary
authors.identifier: 0000-0002-7911-788X
authors.initials: C
authors.lastname: Treda
authors.affiliation: Department of Research and Development, Celther Polska Ltd., Lodz, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Popeda
authors.affiliation: Department of Research and Development, Celther Polska Ltd., Lodz, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Ksiazkiewicz
authors.affiliation: Department of Research and Development, Celther Polska Ltd., Lodz, Poland.
authors.forename: Dawid P
authors.initials: DP
authors.lastname: Grzela
authors.affiliation: Department of Research and Development, Celther Polska Ltd., Lodz, Poland.
authors.forename: Maciej P
authors.initials: MP
authors.lastname: Walczak
authors.affiliation: Department of Research and Development, Celther Polska Ltd., Lodz, Poland.|Department of Tumor Biology, Medical University of Lodz, Lodz, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Banaszczyk
authors.affiliation: Department of Research and Development, Celther Polska Ltd., Lodz, Poland.|Department of Tumor Biology, Medical University of Lodz, Lodz, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Peciak
authors.affiliation: Department of Research and Development, Celther Polska Ltd., Lodz, Poland.|Department of Tumor Biology, Medical University of Lodz, Lodz, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Stoczynska-Fidelus
authors.affiliation: Department of Research and Development, Celther Polska Ltd., Lodz, Poland.|Department of Tumor Biology, Medical University of Lodz, Lodz, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Rieske
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion; D002460:Cell Line; D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human