| First Author | Yang Y | Year | 2008 |
| Journal | PLoS One | Volume | 3 |
| Issue | 5 | Pages | e2220 |
| PubMed ID | 18493606 | Mgi Jnum | J:136369 |
| Mgi Id | MGI:3796038 | Doi | 10.1371/journal.pone.0002220 |
| Citation | Yang Y, 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 |
| abstractText | 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. |
