References
Query Results -- Details
MGI Accession ID: MGI:3639398
J Number: J:110131
Other Accession IDs:
Title: The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies.
Authors: Ji H; Li D; Chen L; Shimamura T; Kobayashi S; McNamara K; Mahmood U; Mitchell A; Sun Y; Al-Hashem R; Chirieac LR; Padera R; Bronson RT; Kim W; Janne PA; Shapiro GI; Tenen D; Johnson BE; Weissleder R; Sharpless NE; Wong KK
Journal: Cancer Cell
Volume: 9
Issue: 6
Date: 2006 Jun
Year: 2006
Pages: 485-95
Review Status: Peer Reviewed
Abstract:
To understand the role of human epidermal growth factor receptor (hEGFR) kinase domain mutations in lung tumorigenesis and response to EGFR-targeted therapies, we generated bitransgenic mice with inducible expression in type II pneumocytes of two common hEGFR mutants seen in human lung cancer. Both bitransgenic lines developed lung adenocarcinoma after sustained hEGFR mutant expression, confirming their oncogenic potential. Maintenance of these lung tumors was dependent on continued expression of the EGFR mutants. Treatment with small molecule inhibitors (erlotinib or HKI-272) as well as prolonged treatment with a humanized anti-hEGFR antibody (cetuximab) led to dramatic tumor regression. These data suggest that persistent EGFR signaling is required for tumor maintenance in human lung adenocarcinomas expressing EGFR mutants.
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