Constitutive achaete-scute homologue-1 promotes airway dysplasia and lung neuroendocrine tumors in transgenic mice.
Constitutive achaete-scute homologue-1 promotes airway dysplasia and lung neuroendocrine tumors in transgenic mice.
复制标题
DOI：
--
复制
发表时间：
2000-08
期刊：
影响因子：
11.2
通讯作者：
R. Linnoila;Bihong Zhao;J. Demayo;B. Nelkin;S. Baylin;F. Demayo;D. Ball
中科院分区：
文献类型：
--
作者：
R. Linnoila;Bihong Zhao;J. Demayo;B. Nelkin;S. Baylin;F. Demayo;D. Ball
转录因子-1(ASH1)是胚胎发育过程中神经分化所必需的，是小细胞肺癌等神经内分泌(NE)肿瘤的主要特征。为了探索ASH1促进NE分化和肺肿瘤发生的可能性，我们利用转基因小鼠在非内分泌呼吸道上皮细胞中结构性地表达了ASH1。在出生3周时开始出现进行性呼吸道增生和化生。ASH1可增强SV40大T抗原在呼吸道上皮细胞中的致瘤作用。这些双转基因动物发生了大量的NE肺癌，这意味着ASH1可能与P53、pRb或相关通路的缺陷协同促进NE肺癌的发生。
The transcription factor achaete-scute homologue-1 (ASH1) is essential for neural differentiation during fetal development and is a cardinal feature of neuroendocrine (NE) tumors such as small cell lung cancer. To explore the potential of ASH1 to promote NE differentiation and tumorigenesis in the lung, we constitutively expressed the factor in nonendocrine airway epithelial cells using transgenic mice. Progressive airway hyperplasia and metaplasia developed beginning at 3 weeks of life. ASH1 potently enhanced the tumorigenic effect of SV40 large T antigen in airway epithelium. These doubly transgenic animals developed massive NE lung tumors, implying that ASH1 may cooperate with defects in p53, pRb, or related pathways in promoting NE lung carcinogenesis.