High expression of ErbB family members and their ligands in lung adenocarcinomas that are sensitive to inhibition of epidermal growth factor receptor

Nobukazu Fujimoto, Marie Wislez, Jie Zhang, Kentaro Iwanaga, Jennifer Dackor, Amy E. Hanna, Shailaja Kalyankrishna, Dianna D. Cody, Roger E. Price, Mitsuo Sato, Jerry W. Shay, John D. Minna, Michael Peyton, Ximing Tang, Erminia Massarelli, Roy Herbst, David W. Threadgill, Ignacio I. Wistuba, Jonathan M. Kurie

Research output: Contribution to journalArticle

125 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)11478-11485
Number of pages8
JournalCancer research
Volume65
Issue number24
DOIs
StatePublished - Dec 15 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Fujimoto, N., Wislez, M., Zhang, J., Iwanaga, K., Dackor, J., Hanna, A. E., Kalyankrishna, S., Cody, D. D., Price, R. E., Sato, M., Shay, J. W., Minna, J. D., Peyton, M., Tang, X., Massarelli, E., Herbst, R., Threadgill, D. W., Wistuba, I. I., & Kurie, J. M. (2005). High expression of ErbB family members and their ligands in lung adenocarcinomas that are sensitive to inhibition of epidermal growth factor receptor. Cancer research, 65(24), 11478-11485. https://doi.org/10.1158/0008-5472.CAN-05-1977