JUN-Mediated Downregulation of EGFR Signaling Is Associated with Resistance to Gefitinib in EGFR-mutant NSCLC Cell Lines.
| Autor: | Kani K; Lawrence J. Ellison Institute for Transformative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California. kani@usc.edu paragm@stanford.edu.; Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California Keck School of Medicine, Los Angeles, California., Garri C; Lawrence J. Ellison Institute for Transformative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California., Tiemann K; Lawrence J. Ellison Institute for Transformative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California., Malihi PD; Lawrence J. Ellison Institute for Transformative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California., Punj V; Division of Hematology, Department of Medicine, University of Southern California, Los Angeles, California., Nguyen AL; Lawrence J. Ellison Institute for Transformative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California., Lee J; Lawrence J. Ellison Institute for Transformative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California., Hughes LD; Lawrence J. Ellison Institute for Transformative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California., Alvarez RM; Lawrence J. Ellison Institute for Transformative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California., Wood DM; Lawrence J. Ellison Institute for Transformative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California., Joo AY; Lawrence J. Ellison Institute for Transformative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California., Katz JE; Lawrence J. Ellison Institute for Transformative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California., Agus DB; Lawrence J. Ellison Institute for Transformative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.; Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California Keck School of Medicine, Los Angeles, California., Mallick P; Lawrence J. Ellison Institute for Transformative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California. kani@usc.edu paragm@stanford.edu.; Department of Radiology, Stanford University, Stanford, California. |
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| Jazyk: | angličtina |
| Zdroj: | Molecular cancer therapeutics [Mol Cancer Ther] 2017 Aug; Vol. 16 (8), pp. 1645-1657. Date of Electronic Publication: 2017 May 31. |
| DOI: | 10.1158/1535-7163.MCT-16-0564 |
| Abstrakt: | Mutations or deletions in exons 18-21 in the EGFR ) are present in approximately 15% of tumors in patients with non-small cell lung cancer (NSCLC). They lead to activation of the EGFR kinase domain and sensitivity to molecularly targeted therapeutics aimed at this domain (gefitinib or erlotinib). These drugs have demonstrated objective clinical response in many of these patients; however, invariably, all patients acquire resistance. To examine the molecular origins of resistance, we derived a set of gefitinib-resistant cells by exposing lung adenocarcinoma cell line, HCC827, with an activating mutation in the EGFR tyrosine kinase domain, to increasing gefitinib concentrations. Gefitinib-resistant cells acquired an increased expression and activation of JUN, a known oncogene involved in cancer progression. Ectopic overexpression of JUN in HCC827 cells increased gefitinib IC (©2017 American Association for Cancer Research.) |
| Databáze: | MEDLINE |
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