[HTML][HTML] Phosphatidylinositol 3-Kinase Mediates Bronchioalveolar Stem Cell Expansion in Mouse Models of Oncogenic K-ras-Induced Lung Cancer
PloS one, 2008•journals.plos.org
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 …
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 …
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.
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