Epidermal growth factor receptor status and Notch inhibition in non-small cell lung cancer cells.
BACKGROUND
Notch may behave as an oncogene or a tumor suppressor gene in lung cancer cells. Notch receptor undergoes cleavage by enzymes, including γ-secretase, generating the active Notch intracellular domain (NICD). The aim of the present study was to investigate the effect of DAPT, a γ-secretase inhibitor, in non-small cell lung cancer (NSCLC) cells, as well as the impact of epidermal growth factor (EGF) that is over-expressed by NSCLC cells, on Notch signaling. H23, A549, H661 and HCC827 human NSCLC cell lines were used, expressing various NICD and EGF receptor (EGFR) protein levels.


RESULTS
DAPT decreased the number of H661 cells in a concentration-dependent manner, while it had a small effect on H23 and A549 cells and no effect on HCC827 cells that carry mutated EGFR. Notch inhibition did not affect the stimulatory effect of EGF on cell proliferation, while EGF prevented DAPT-induced NICD decrease in H23 and H661 cells. The type of cell death induced by DAPT seems to depend on the cell type.


CONCLUSIONS
Our data indicate that inhibition of Notch cleavage may not affect cell number in the presence of EGFR mutations and that EGFR may affect Notch signalling suggesting that a dual inhibition of these pathways might be promising in NSCLC.
Clinical Oncology Laboratory, Division of Oncology, Department of Medicine, University of Patras, Patras Medical School, Rio, 26504, Greece.
Efstathia
E
Giannopoulou
Clinical Oncology Laboratory, Division of Oncology, Department of Medicine, University of Patras, Patras Medical School, Rio, 26504, Greece.
Achilleas
A
Nikolakopoulos
Clinical Oncology Laboratory, Division of Oncology, Department of Medicine, University of Patras, Patras Medical School, Rio, 26504, Greece.|Laboratory of Molecular Pharmacology, Department of Pharmacy, School of Health Science, University of Patras, Rio, 26504, Greece.
Dimitra
D
Kotsirilou
Clinical Oncology Laboratory, Division of Oncology, Department of Medicine, University of Patras, Patras Medical School, Rio, 26504, Greece.|Laboratory of Biochemistry, Department of Chemistry, University of Patras, Rio, 26504, Greece.
Angeliki
A
Lampropoulou
Electron Microscopy Laboratory, Faculty of Crop Production, Agricultural University of Athens, Iera Odos 75, Athens, 11855, Greece.
Sofia
S
Raftopoulou
Laboratory of Molecular Pharmacology, Department of Pharmacy, School of Health Science, University of Patras, Rio, 26504, Greece.
Evangelia
E
Papadimitriou
Laboratory of Biochemistry, Department of Chemistry, University of Patras, Rio, 26504, Greece.
Achilleas D
AD
Theocharis
Clinical Oncology Laboratory, Division of Oncology, Department of Medicine, University of Patras, Patras Medical School, Rio, 26504, Greece.
Thomas
T
Makatsoris
Electron Microscopy Laboratory, Faculty of Crop Production, Agricultural University of Athens, Iera Odos 75, Athens, 11855, Greece.
Konstantinos
K
Fasseas
Clinical Oncology Laboratory, Division of Oncology, Department of Medicine, University of Patras, Patras Medical School, Rio, 26504, Greece. kalofonos@upatras.gr.
Haralabos P
HP
Kalofonos
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D051880:Receptors, Notch; D025521:Tumor Suppressor Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors