Mutationally-activated PI3'-kinase-α promotes de-differentiation of lung tumors initiated by the BRAF^V600E oncoprotein kinase.

ABSTRACT: Human lung adenocarcinoma exhibits a propensity for de-differentiation, complicating diagnosis and treatment, and predicting poorer patient survival. In genetically engineered mouse models of lung cancer, expression of the BRAF^V600E oncoprotein kinase initiates the growth of benign tumors retaining characteristics of their cell of origin, AT2 pneumocytes. Cooperating alterations that activate PI3'-lipid signaling promote progression of BRAF^V600E-driven benign tumors to malignant adenocarcinoma. However, the mechanism(s) by which this cooperation occurs remains unclear. To address this, we generated mice carrying a conditional Braf^CAT allele in which CRE-mediated recombination leads to co-expression of BRAF^V600E and tdTomato. We demonstrate

SUBMITTER: van Veen JE 

PROVIDER: S-EPMC6711745 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature