An EGFR ligand promotes EGFR-mutant but not KRAS-mutant lung cancer in vivo
| Autor: | Iris M. Fink-Baldauf, Tomoshi Tsuchiya, Yutaka Maeda, Takuya Fukazawa, Minzhe Guo, Yoshio Naomoto, Koichi Tomoshige, Takeshi Nagayasu, William D. Stuart |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genetically modified mouse Cancer Research TGF alpha Lung Neoplasms AGR2 Adenocarcinoma of Lung Mice Transgenic Biology medicine.disease_cause Ligands Proto-Oncogene Proteins p21(ras) 03 medical and health sciences Mice In vivo Cell Line Tumor Genetics medicine Animals Humans Lung cancer Molecular Biology Lung Proteins respiratory system medicine.disease respiratory tract diseases ErbB Receptors stomatognathic diseases 030104 developmental biology medicine.anatomical_structure Mutation Cancer research Adenocarcinoma KRAS |
| Zdroj: | Oncogene. 37(28) |
| ISSN: | 1476-5594 |
| Popis: | EGFR ligands (e.g., EGF and TGFA) have been shown to be clinically associated with poor survival in lung cancer. Since TGFA itself initiates autochthonous tumors in liver, breast, and pancreas but not in the lung in transgenic mice in vivo, it would appear that an EGFR ligand may not initiate but rather promote lung cancer. However, it has not been proven in vivo whether lung cancer is promoted by an EGFR ligand. Using transgenic mouse models conditionally expressing EGFRL858R or KrasG12D with TGFA (an EGFR ligand) in lung epithelium, we determined that TGFA promoted the growth of EGFRL858R-lung tumors in airway regions but not that of KrasG12D-lung tumors. Analysis of TCGA datasets identified ΔNp63 and AGR2 as potential key tumor-promoting regulators, which were highly induced in the TGFA-induced EGFRL858R-lung tumors. The expression of AGR2 was positively correlated with the expression of TGFA in human EGFR-mutant lung adenocarcinomas. The expression of TGFA in human EGFR-mutant lung adenocarcinomas but not in the EGFR wild-type lung adenocarcinoma was associated with poor survival. These results suggest that targeting EGFR ligands may benefit patients who carry EGFR-mutant lung tumors but will not benefit patients with KRAS-mutant lung tumors. |
| Databáze: | OpenAIRE |
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