EGF Receptor Signaling Is Essential for K-Ras Oncogene-Driven Pancreatic Ductal Adenocarcinoma
Menées sur des modèles murins, ces deux études mettent en évidence le rôle essentiel joué par la signalisation EGFR dans les cancers du pancréas associés à des mutations activant l'expression du gène KRAS
Clinical evidence indicates that mutation/activation of EGF receptors (EGFRs) is mutually exclusive with the presence of K-RAS oncogenes in lung and colon tumors. We have validated these observations using genetically engineered mouse models. However, development of pancreatic ductal adenocarcinomas driven by K-Ras oncogenes are totally dependent on EGFR signaling. Similar results were obtained using human pancreatic tumor cell lines. EGFRs were also essential even in the context of pancreatic injury and absence of p16Ink4a/p19Arf. Only loss of p53 made pancreatic tumors independent of EGFR signaling. Additional inhibition of PI3K and STAT3 effectively prevented proliferation of explants derived from these p53-defective pancreatic tumors. These findings may provide the bases for more rational approaches to treat pancreatic tumors in the clinic. º Pancreatic injury induces expression of EGFRs in acinar cells º EGFR signaling is essential for PanIN and PDAC development induced by K-Ras oncogenes º Loss of senescence by ablation of p16Ink4a/p19Arf does not abrogate EGFR dependence º Loss of p53 makes PDAC tumors independent of EGFR signaling
Cancer cell , résumé, 2011