Significance of Notch signaling in cell fact determination of lung

Notch信号通路在决定各种细胞系统的细胞命运中起着重要作用，被认为在肺上皮细胞和肺癌的细胞命运决定中起作用。该途径通过调节原基螺旋环螺旋因子网络起作用。我们做了一些实验研究来阐明Notch通路在肺中的意义，得到了以下结果。1)免疫组织化学和Northern blot结果显示，小鼠肺神经内分泌细胞（PNEC）的Mash1、Hes1（胞浆染色）、Delta-like1（DII-1）呈阳性，而非PNEC的肺神经内分泌细胞（PNEC）的Hes1（核与胞浆染色）、Notch-3、Jagged1-2呈阳性。Mash1基因缺失小鼠肺中未检测到DII-1表达，Hes1基因缺失小鼠肺中Notch1表达降低。2)在人肺癌细胞系中，小细胞癌细胞表达hASH1、Hes1、DII-1、Jag1和Jag2，非小细胞癌细胞表达Hes1、Notch1-Notch3和Jag1。3)转染Notch1基因和Notch1基因胞质内结构域抑制细胞增殖速率，抑制神经内分泌分化，诱导上皮形态，增强细胞黏附性。因此，这些研究支持Notch信号通路和基本的螺旋-环-螺旋因子网络可能在人类肺部疾病的细胞分化调控中起重要作用。

The Notch signaling pathway plays an important role in determining cell fate of various cell system, and is considered to function in cell fate determination of the lung epithelia and lung carcinoma. And, the pathway works through regulating the network of proneural basic helix-loop helix factors.We did some experimental studies to clarify the significance of the Notch pathway in the lung, and gained the following results. 1) Immunohistochemical and Northern blot studies revealed that pulmonary neuroendocrine cells of the mouse (PNEC) showed positive staining for Mash1, Hes1(Cytoplasmic stain), Delta-like1(DII-1), but non-PNEC showed positive staining for Hes1 (nuclear and cytoplasmic stain), Notch-3, Jagged1-2. Expression of DII-1 is not detected in the lungs of Mash1 gene null mice, and expression of Notch1 is decreased in the lung of Hes1 gene null mice. 2) In human lung cancer cell lines, small cell carcinoma cells expressed hASH1, Hes1, DII-1, Jag1, and Jag2, but non-small cell carcinoma cells expressed Hes1, Notch1-Notch3, and Jag1. 3) Transfection of Notch1 gene and intracytoplasmic domain of Notch1 gene suppressed cell proliferation rate, abolished neuroendocrine differentiation and induced epithelial morphology with enhanced cell adhesiveness.Thus, theses studies support that the Notch signaling pathway and the basic helix-loop-helix factor network could be important in cell differentiation regulation in human lung diseases.