Phosphatidylinositol 3-Kinase Mediates Bronchioalveolar Stem Cell Expansion in Mouse Models of Oncogenic K-ras-Induced Lung Cancer

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Author
Yang, Yanan
Iwanaga, Kentaro
Raso, Maria Gabriela
Wislez, Marie
Hanna, Amy E.
Wieder, Eric D.
Molldrem, Jeffrey J.
Wistuba, Ignacio I.
Powis, Garth
Demayo, Francesco J.
Kurie, Jonathan M.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1371/journal.pone.0002220Metadata
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Yang, 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.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. 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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2376060/pdf/Terms of Use
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