Shieh Yi-Shing, Lai Chiung-Ya, Kao Yu-Rung, Shiah Shine-Gwo, Chu Yi-Wen, Lee Herng-Sheng, Wu Cheng-Wen
School of Dentistry, National Defense Medical Center, Taipei, Taiwan, ROC.
Neoplasia. 2005 Dec;7(12):1058-64. doi: 10.1593/neo.05640.
We used the Transwell system to select highly invasive cell lines from minimally invasive parent cells, and we compared gene expression in paired cell lines with high and low invasive potentials. Axl was relatively overexpressed in the highly invasive cell lines when compared with their minimally invasive counterparts. However, there is only limited information about the role of Axl in cancer invasion. The biologic function of Axl in tumor invasion was investigated by overexpression of full-length Axl in minimally invasive cells and by siRNA knockdown of Axl expression in highly invasive cells. Overexpression of Axl in minimally invasive cells increased their invasiveness. siRNA reduced cell invasiveness as Axl was downregulated in highly invasive cells. We further investigated the protein expression of Axl by immunohistochemistry and its correlation with clinicopathologic features. Data from a study of 58 patient specimens showed that Axl immunoreactivity was statistically significant with respect to lymph node status (P < .0001) and the patient's clinical stage (P < .0001). Our results demonstrate that Axl protein kinase seems to play an important role in the invasion and progression of lung cancer.
我们使用Transwell系统从微创亲本细胞中筛选出高侵袭性细胞系，并比较了具有高侵袭潜能和低侵袭潜能的配对细胞系中的基因表达。与微创对应细胞系相比，Axl在高侵袭性细胞系中相对过表达。然而，关于Axl在癌症侵袭中的作用的信息有限。通过在微创细胞中过表达全长Axl以及在高侵袭性细胞中通过小干扰RNA（siRNA）敲低Axl表达，研究了Axl在肿瘤侵袭中的生物学功能。在微创细胞中过表达Axl增加了它们的侵袭性。当Axl在高侵袭性细胞中被下调时，siRNA降低了细胞侵袭性。我们通过免疫组织化学进一步研究了Axl的蛋白表达及其与临床病理特征的相关性。对58例患者标本的研究数据表明，Axl免疫反应性在淋巴结状态（P < .0001）和患者临床分期（P < .0001）方面具有统计学意义。我们的结果表明，Axl蛋白激酶似乎在肺癌的侵袭和进展中起重要作用。
