Abstract 4168: Mig-6 ablation cooperates with oncogenic Kras in promoting mouse lung tumorigenesis

Abstract

Abstract Lung tumorigenesis is a stochastic multistep process, during which different gene mutations accumulate, and Kras is an oncogene with the most frequent mutation in the Caucasian lung adenocarcinoma. Although Mig-6 (mitogen-inducible gene 6) has been shown to be a tumor suppressor gene in lung, skin and uterus, the interplay between Mig-6 and Kras in lung tumorigenesis remains elusive. Here, we found Mig-6 expression was down-regulated in oncogenic KrasG12D-induced lung tumors and Mig-6d/dKrasG12D mice showed an earlier onset of pulmonary tumor development and a significantly reduced life span as compared to KrasG12D mice though no obvious lung phenotype was observed in Mig-6d/d mice. Meanwhile, ablation of Mig-6 can change the lung epithelial cell fate in KrasG12D mice. Furthermore, lung tumor tissues of Mig-6d/dKrasG12D mice showed decreased cellular apoptosis, elevated EGF/Akt signaling and increased severity of inflammation as compared to those of KrasG12D mice. Thus, ablation of Mig-6 cooperated with oncogenic Kras in promoting lung tumorigenesis and this novel murine model of lung cancer can be applied for future study. Citation Format: Jian Liu, Sung-Nam Cho, Nili Jin, Seyed Javad Moghaddam, Jennifer Gilbert, Ignacio Wistuba, Francesco J. DeMayo. Mig-6 ablation cooperates with oncogenic Kras in promoting mouse lung tumorigenesis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4168.