PTEN is a Potent Suppressor of Small Cell Lung Cancer.

Publication Type:

Journal Article

Source:

Molecular cancer research : MCR, Volume 12, Issue 5, p.654-9 (2014)

Keywords:

2014, Center-Authored Paper, Comparative Medicine Core Facility, Experimental Histopathology Core Facility, February 2014, Human Biology Division, Scientific Imaging Core Facility, Shared Resources

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 to 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 non-metastatic adenocarcinoma with neuroendocrine differentiation. This study reveals a critical role for the PTEN/PI3-kinase pathway in both SCLC and lung adenocarcinoma and provides an ideal system to test PI3-kinase pathway inhibitors as targeted therapy for subsets of SCLC patients. 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 SCLC patients.