PTEN is a potent suppressor of small cell lung cancer.
PTEN is a potent suppressor of small cell lung cancer.
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DOI：
10.1158/1541-7786.mcr-13-0554
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发表时间：
2014-05
期刊：
影响因子：
--
通讯作者：
MacPherson D
中科院分区：
文献类型：
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作者：
Cui M;Augert A;Rongione M;Conkrite K;Parazzoli S;Nikitin AY;Ingolia N;MacPherson D
小细胞肺癌(SCLC)是一种高转移性肿瘤，具有神经内分泌特征，预后不良。PTEN突变和PIK3CA激活突变在小细胞肺癌中已有报道，但该通路的功能相关性尚不清楚。利用含有失活Rb和P53的AdenoCre驱动的小鼠SCLC模型，询问PTEN/PIK3CA通路。在Rb/P53缺失的小鼠中，PTEN的一个等位基因失活导致小细胞肺癌加速，并经常发生肝脏转移。与人类小细胞肺癌报告的高突变负担相反，外显子组分析显示小鼠小细胞肺癌中蛋白质改变突变的数量很少。Rb/P53缺失系统中PTEN两个等位基因的失活导致具有神经内分泌分化的非转移性腺癌。这项研究揭示了PTEN/PI3-激酶通路在小细胞肺癌和肺腺癌中的关键作用，并提供了一种理想的系统来测试PI3-激酶通路抑制剂作为小细胞肺癌患者亚群的靶向治疗。
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.