Yang, YananIwanaga, KentaroRaso, Maria GabrielaWislez, MarieHanna, Amy E.Wieder, Eric D.Molldrem, Jeffrey J.Wistuba, Ignacio I.Powis, GarthDemayo, Francesco J.Kurie, Jonathan M.Kim, Carla2013-01-182008Yang, Yanan, Kentaro Iwanaga, Maria Gabriela Raso, Marie Wislez, Amy E. Hanna, Eric D. Wieder, Jeffrey J. Molldrem, et al. 2008. Phosphatidylinositol 3-kinase mediates bronchioalveolar stem cell expansion in mouse models of oncogenic K-ras-induced lung cancer. PLoS ONE 3(5): e2220.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:10198685Background: Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death in Western countries. Developing more effective NSCLC therapeutics will require the elucidation of the genetic and biochemical bases for this disease. Bronchioalveolar stem cells (BASCs) are a putative cancer stem cell population in mouse models of oncogenic K-ras-induced lung adenocarcinoma, an histologic subtype of NSCLC. The signals activated by oncogenic K-ras that mediate BASC expansion have not been fully defined. Methodology/Principal Findings: We used genetic and pharmacologic approaches to modulate the activity of phosphatidylinositol 3-kinase (PI3K), a key mediator of oncogenic K-ras, in two genetic mouse models of lung adenocarcinoma. Oncogenic K-ras-induced BASC accumulation and tumor growth were blocked by treatment with a small molecule PI3K inhibitor and enhanced by inactivation of phosphatase and tensin homologue deleted from chromosome 10, a negative regulator of PI3K. Conclusions/Significance: We conclude that PI3K is a critical regulator of BASC expansion, supporting treatment strategies to target PI3K in NSCLC patients.en-USJournal Article2013-01-1810.1371/journal.pone.0002220