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Model Characteristics - Model:
Bronchial and Peripheral Murine Lung Carcinomas Induced
by T790M-L858R Mutant EGFR Respond to HKI-272 and
Rapamycin Combination Therapy
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| Model Descriptor |
Bronchial and Peripheral Murine Lung Carcinomas Induced
by T790M-L858R Mutant EGFR Respond to HKI-272 and
Rapamycin Combination Therapy
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| Official Nomenclature |
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| Genotype |
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| Species |
Mouse (Mus musculus)
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| Strain |
FVB/N
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| Is This a Tool Strain? |
No
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Developmental Stage
(applies only to Zebrafish) |
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| Experimental Design |
The EGFR T790M mutation has been identified in tumors from lung cancer patients that eventually develop resistance to erlotinib. In this study, we generated a mouse model with doxycycline-inducible expression of a mutant EGFR containing both L858R, an erlotinib-sensitizing mutation, and the T790M resistance mutation (EGFR TL). Expression of EGFR TL led to development of peripheral adenocarcinomas with bronchioloalveolar features in alveoli as well as papillary adenocarcinomas in bronchioles.brbr
To generate the Tet-op-EGFR TL transgenic mice, site-directed mutagenesis was performed on the pCIBA-hEGFR plasmid. The fragment containing the whole hEGFR ORF with the Kozak site was then subcoloned into pTRE2-hyg. The constructs were then digested to release the entire allele containing Tet-op-EGFR TL-¿-globin polyA. Transgenic mice were then generated by injection of the construct into FVB/N blastocysts. Progeny were genotyped and characterized.
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| Phenotype |
Treatment with an irreversible EGFR tyrosine kinase inhibitor (TKI), HKI-272, shrunk only peripheral tumors but not bronchial tumors. However, the combination of HKI-272 and rapamycin resulted in significant regression of both types of lung tumors. This combination therapy may potentially benefit lung cancer patients with the EGFR T790M mutation.
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| Website for add. info |
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| Breeding Notes |
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| Sex Distribution of the Phenotype |
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| Submitted by |
caMOD, Curator
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| Principal Investigator / Lab |
Wong*, Kwok-Kin
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| Comment |
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| Model Availability: This model is available from |
| Strain |
Distributor |
Stock number |
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