title: High expression of ErbB family members and their ligands in lung adenocarcinomas that are sensitive to inhibition of epidermal growth factor receptor.
abstract: Recent findings in tumor biopsies from lung adenocarcinoma patients suggest that somatic mutations in the genes encoding epidermal growth factor receptor (EGFR) and Kirsten ras (KRAS) confer sensitivity and resistance, respectively, to EGFR inhibition. Here, we provide evidence that these genetic mutations are not sufficient to modulate the biological response of lung adenocarcinoma cells to EGFR inhibition. We found high expression of ErbB family members, ErbB ligands, or both in three models that were sensitive to EGFR inhibition, including alveolar epithelial neoplastic lesions in mice that develop lung adenocarcinoma by oncogenic KRAS, human lung adenocarcinoma cell lines, and tumor biopsies from lung adenocarcinoma patients. Thus, lung adenocarcinoma cells that depend on EGFR for survival constitutively activate the receptor through a combination of genetic mutations and overexpression of EGFR dimeric partners and their ligands.
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, 77030, USA.
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Fujimoto
authors.forename: Marie
authors.initials: M
authors.lastname: Wislez
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Kentaro
authors.initials: K
authors.lastname: Iwanaga
authors.forename: Jennifer
authors.initials: J
authors.lastname: Dackor
authors.forename: Amy E
authors.initials: AE
authors.lastname: Hanna
authors.forename: Shailaja
authors.initials: S
authors.lastname: Kalyankrishna
authors.forename: Dianna D
authors.initials: DD
authors.lastname: Cody
authors.forename: Roger E
authors.initials: RE
authors.lastname: Price
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Sato
authors.forename: Jerry W
authors.initials: JW
authors.lastname: Shay
authors.forename: John D
authors.initials: JD
authors.lastname: Minna
authors.forename: Michael
authors.initials: M
authors.lastname: Peyton
authors.forename: Ximing
authors.initials: X
authors.lastname: Tang
authors.forename: Erminia
authors.initials: E
authors.lastname: Massarelli
authors.forename: Roy
authors.initials: R
authors.lastname: Herbst
authors.forename: David W
authors.initials: DW
authors.lastname: Threadgill
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Kurie
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077156:Gefitinib; D011905:Genes, ras / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008024:Ligands; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009375:Neoplasms, Glandular and Epithelial / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000077156:Gefitinib; D008024:Ligands; D051057:Proto-Oncogene Proteins c-akt; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D014443:Tyrosine