Induction of lung adenocarcinoma in transgenic mice expressing activated EGFR driven by the SP-C promoter

Kadoaki Ohashi, Kammei Rai, Yoshiro Fujiwara, Masahiro Osawa, Seiki Hirano, Katsuyoshi Takata, Eisaku Kondo, Tadashi Yoshino, Minoru Takata, Mitsune Tanimoto, Katsuyuki Kiura

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)


To investigate the role of an activating epidermal growth factor receptor (EGFR) mutation in lung cancer, we generated transgenic mice expressing the delE748-A752 mutant version of mouse EGFR driven by the SP-C promoter, which is equivalent to the delE746-A750 mutation found in lung cancer patients. Strikingly, the mice invariably developed multifocal lung adenocarcinomas of varying sizes at between 5 and 6 weeks of age, and they died from tumor progression approximately 2 months later if left untreated. Daily oral administration of the EGFR tyrosine kinase inhibitor (TKI) gefitinib (5 mg/kg/day) reduced the total and phosphorylation levels of EGFR to those in wild-type mouse lung tissue; in addition, it abrogated tumor growth within 1 week and prolonged survival to >30 weeks. Interestingly, phosphorylated ErbB2, ErbB3, and thyroid transcriptional factor-1 increased in the transgenic mice compared with those in wild-type mice. They might play some roles in tumors progression in the transgenic mice. This model will be useful for studying the mechanisms of carcinogenesis, chemoprevention, and acquired resistance to EGFR TKIs in lung cancer patients carrying activating EGFR mutations.

Original languageEnglish
Pages (from-to)1747-1753
Number of pages7
JournalCancer Science
Issue number9
Publication statusPublished - 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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