title: Phosphatidylinositol 3-kinase mediates bronchioalveolar stem cell expansion in mouse models of oncogenic K-ras-induced lung cancer.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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
  We conclude that PI3K is a critical regulator of BASC expansion, supporting treatment strategies to target PI3K in NSCLC patients.
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Yang
authors.forename: Kentaro
authors.initials: K
authors.lastname: Iwanaga
authors.forename: Maria Gabriela
authors.initials: MG
authors.lastname: Raso
authors.forename: Marie
authors.initials: M
authors.lastname: Wislez
authors.forename: Amy E
authors.initials: AE
authors.lastname: Hanna
authors.forename: Eric D
authors.initials: ED
authors.lastname: Wieder
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Molldrem
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.forename: Garth
authors.initials: G
authors.lastname: Powis
authors.forename: Francesco J
authors.initials: FJ
authors.lastname: Demayo
authors.forename: Carla F
authors.initials: CF
authors.lastname: Kim
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Kurie
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000818:Animals; D001980:Bronchi / Q000473:pathology*; D004195:Disease Models, Animal; D011905:Genes, ras; D006067:Gonanes / Q000494:pharmacology; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000473:pathology*; D013234:Stem Cells / Q000166:cytology*
chemical_list: D006067:Gonanes; C496788:PX-866; D019869:Phosphatidylinositol 3-Kinases