Adenocarcinoma of the lung, a leading cause of cancer death, frequently displays mutational activation of the KRAS proto-oncogene but, unlike lung cancers expressing mutated EGFR, ROS1 or ALK, there is no pathway-targeted therapy for patients with KRAS mutated lung cancer. In pre-clinical models, expression of oncogenic KRASG12D in the lung epithelium of adult mice initiates development of lung adenocarcinoma through activation of downstream signaling pathways. By contrast, mutationally activated BRAFV600E, a KRAS effector, fails to initiate lung carcinogenesis despite highly efficient induction of benign lung tumorigenesis. To test if PI3'-kinase-α(PIK3CA), another KRAS effector, might cooperate with oncogenic BRAFV600E to promote lung cancer progression, we employed mice carrying a conditional allele of Pik3ca that allows conversion of the wild-type catalytic subunit of PIK3CA to mutationally activated PIK3CAH1047R. Whereas expression of PIK3CAH1047R in the lung epithelium, either alone or in combination with PTEN silencing, was without phenotype, concomitant expression of BRAFV600E and PIK3CAH1047R led to dramatically decreased tumor latency and increased tumor burden compared to BRAFV600E alone. Most notably, co-expression of BRAFV600E and PIK3CAH1047R elicited lung adenocarcinomas in a manner reminiscent of the effects of KRASG12D. These data emphasize a role for PI3'-kinase signaling, not in lung tumor initiation per se, but in both the rate of tumor growth and the propensity of benign lung tumors to progress to a malignant phenotype. Finally, biological and biochemical analysis of BRAFV600E/PIK3CAH1047R expressing mouse lung cancer cells revealed mechanistic clues as to cooperative regulation of the cell division cycle and apoptosis by these oncogenes.