TY - JOUR
T1 - High expression of ErbB family members and their ligands in lung adenocarcinomas that are sensitive to inhibition of epidermal growth factor receptor
AU - Fujimoto, Nobukazu
AU - Wislez, Marie
AU - Zhang, Jie
AU - Iwanaga, Kentaro
AU - Dackor, Jennifer
AU - Hanna, Amy E.
AU - Kalyankrishna, Shailaja
AU - Cody, Dianna D.
AU - Price, Roger E.
AU - Sato, Mitsuo
AU - Shay, Jerry W.
AU - Minna, John D.
AU - Peyton, Michael
AU - Tang, Ximing
AU - Massarelli, Erminia
AU - Herbst, Roy
AU - Threadgill, David W.
AU - Wistuba, Ignacio I.
AU - Kurie, Jonathan M.
PY - 2005/12/15
Y1 - 2005/12/15
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-05-1977
DO - 10.1158/0008-5472.CAN-05-1977
M3 - Article
C2 - 16357156
AN - SCOPUS:29244450494
SN - 0008-5472
VL - 65
SP - 11478
EP - 11485
JO - Cancer Research
JF - Cancer Research
IS - 24
ER -