High expression of ErbB family members and their ligands in lung adenocarcinomas that are sensitive to inhibition of epidermal growth factor receptor.
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.
Fujimoto
Nobukazu
N
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, 77030, USA.
Wislez
Marie
M
Zhang
Jie
J
Iwanaga
Kentaro
K
Dackor
Jennifer
J
Hanna
Amy E
AE
Kalyankrishna
Shailaja
S
Cody
Dianna D
DD
Price
Roger E
RE
Sato
Mitsuo
M
Shay
Jerry W
JW
Minna
John D
JD
Peyton
Michael
M
Tang
Ximing
X
Massarelli
Erminia
E
Herbst
Roy
R
Threadgill
David W
DW
Wistuba
Ignacio I
II
Kurie
Jonathan M
JM
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
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