PTEN is a potent suppressor of small cell lung cancer

M Cui, A Augert, M Rongione, K Conkrite… - Molecular Cancer …, 2014 - AACR
M Cui, A Augert, M Rongione, K Conkrite, S Parazzoli, AY Nikitin, N Ingolia, D MacPherson
Molecular Cancer Research, 2014AACR
Small cell lung carcinoma (SCLC) is a highly metastatic tumor type with neuroendocrine
features and a dismal prognosis. PTEN mutations and PIK3CA activating mutations have
been reported in SCLC but the functional relevance of this pathway is unknown. The
PTEN/PIK3CA pathway was interrogated using an AdenoCre-driven mouse model of SCLC
harboring inactivated Rb and p53. Inactivation of one allele of PTEN in Rb/p53-deleted mice
led to accelerated SCLC with frequent metastasis to the liver. In contrast with the high …
Abstract
Small cell lung carcinoma (SCLC) is a highly metastatic tumor type with neuroendocrine features and a dismal prognosis. PTEN mutations and PIK3CA activating mutations have been reported in SCLC but the functional relevance of this pathway is unknown. The PTEN/PIK3CA pathway was interrogated using an AdenoCre-driven mouse model of SCLC harboring inactivated Rb and p53. Inactivation of one allele of PTEN in Rb/p53-deleted mice led to accelerated SCLC with frequent metastasis to the liver. In contrast with the high mutation burden reported in human SCLC, exome analyses revealed a low number of protein-altering mutations in mouse SCLC. Inactivation of both alleles of PTEN in the Rb/p53-deleted system led to nonmetastatic adenocarcinoma with neuroendocrine differentiation. This study reveals a critical role for the PTEN/PI3K pathway in both SCLC and lung adenocarcinoma and provides an ideal system to test the phosphoinositide 3-kinase (PI3K) pathway inhibitors as targeted therapy for subsets of patients with SCLC.
Implications: The ability of PTEN inactivation to accelerate SCLC in a genetic mouse model suggests that targeting the PTEN pathway is a therapeutic option for a subset of human patients with SCLC.
Visual Overview: http://mcr.aacrjournals.org/content/early/2014/04/28/1541-7786.MCR-13-0554/F1.large.jpg. Mol Cancer Res; 12(5); 654–9. ©2014 AACR.
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