Division of Molecular Genetics, Centre for Biomedical Genetics, Cancer Genomics Centre, The Netherlands Cancer Institute, Amsterdam.
Cancer Cell. 2011 Jun 14;19(6):754-64. doi: 10.1016/j.ccr.2011.04.019.
Small cell lung cancer (SCLC) is one of the most lethal human malignancies. To investigate the cellular origin(s) of this cancer, we assessed the effect of Trp53 and Rb1 inactivation in distinct cell types in the adult lung using adenoviral vectors that target Cre recombinase to Clara, neuroendocrine (NE), and alveolar type 2 (SPC-expressing) cells. Using these cell type-restricted Adeno-Cre viruses, we show that loss of Trp53 and Rb1 can efficiently transform NE and SPC-expressing cells leading to SCLC, albeit SPC-expressing cells at a lesser efficiency. In contrast, Clara cells were largely resistant to transformation. The results indicate that although NE cells serve as the predominant cell of origin of SCLC a subset of SPC-expressing cells are also endowed with this ability.
小细胞肺癌（SCLC）是人类最致命的恶性肿瘤之一。为了研究这种癌症的细胞起源，我们使用靶向 Cre 重组酶的腺病毒载体评估了 Trp53 和 Rb1 失活对成年肺部不同细胞类型的影响。利用这些细胞类型特异性的 Adeno-Cre 病毒，我们发现 Trp53 和 Rb1 的缺失可以有效地转化 NE 和 SPC 表达细胞，导致 SCLC 的发生，尽管 SPC 表达细胞的效率较低。相比之下，Clara 细胞则基本不受转化影响。结果表明，虽然 NE 细胞是 SCLC 的主要起源细胞，但一部分 SPC 表达细胞也具有这种能力。
