MTA1基因同小细胞肺癌生物学行为的相关性研究

Correlation between MTA1 gene and biological behavior of small cell lung cancer

目的:通过研究人小细胞肺癌(SCLC)及正常肺组织芯片、肺癌细胞系及肿瘤转移相关蛋白1(MTA1)转基因小鼠,明确SCLC中肿瘤转移相关蛋白1的表达及功能机制。方法:采用免疫组化及免疫印迹分析明确SCLC组织芯片以及MTA1转基因小鼠肺组织MTA1和干细胞转录因子2的表达;检测MTA1-siRNA下调SCLC细胞系中MTA1表达后细胞表型的变化。结果:在SCLC组织芯片及细胞系中MTA1呈高表达状态(P<0.05),其表达量在性别、年龄、肿瘤TNM分期各亚组中无显著差异(P>0.05)。SCLC中下调MTA1表达,肿瘤增殖能力显著降低(P<0.05)。SCLC中下调MTA1表达,肿瘤恶性生物学潜能显著降低。MTA1通过调控干细胞转录因子2参与SCLC的恶性生物学进程。结论:MTA1在SCLC中作为关键调控因子可能涉及肿瘤干细胞调控,并且在SCLC的增殖、凋亡方面具有显著影响。

Objective： The expression and functional mechanism of MTA1 in small cell lung cancer （SCLC） were explained by studying human SCLC and normal lung tissue specimens, lung cancer cell line and MTA1 transgenic mouse. Methods：Immunohistochemistry and western blot were used to clarify the expression level of MTA1 and SOX2 in SCLC tissue specimens and MTA1 transgenic mouse. After knocking down the MTA1 by specific MTAI-siRNA sequence, the biological consequence were evaluated. Results： MTA1 shows high expression in tissue and cell line of small cell lung cancer（P〈0.05） and there was no significant difference in the gender, age and TNM staging（P〉0.05） . Compared with MTA1-NC group, MTAI-siRNA group was significantly reduced in cell proliferation of the lung cancer （P〈0.05） . MTA1 downregulation suppresses potential of tumor malignant biological potential of the SCLC cell line. MTA1 was involved in the regulation of malignant biological processes in SCLC by regulating SOX2. Conclusion： MTA1 plays a critical role in regulating the malignant behaviors of SCLC and it is closely related to tumor stem cell regulation. It has significant influence on proliferation and apoptosis of SCLC.