抗增殖蛋白TOB1影响乳腺癌细胞MDA-MB-231体外转移的作用研究

目的研究抗增殖蛋白家族成员TOB1对乳腺癌细胞MDA-MB-231体外侵袭与转移的生物学作用与机制。方法采用脂质体介导的质粒转染和G418筛选培养法获得稳定高表达TOB1的高转移性乳腺癌细胞系MDA-MB-231。通过人工基底膜侵袭实验和划痕实验检测TOB1过表达对MDA-MB-231细胞体外侵袭能力和转移能力的影响。采用super array基因芯片法检测TOB1引起的肿瘤转移相关基因表达的变化。结果与对照组相比,外源性TOB1高水平表达使MDA-MB-231的体外侵袭能力显著降低（P〈0.05）,同时抑制MDA-MB-231的体外迁移能力;TOB1表达水平的增加引起MDA-MB-231细胞中肿瘤转移抑制基因BRMS1表达的明显增加,同时显著抑制肿瘤转移相关基因HSP90、FXYD5、RHOC、S100A4等的表达（均P〈0.05）。结论 TOB1过表达抑制乳腺癌细胞MDA-MB-231的体外侵袭、转移,涉及的机制可能与TOB1对多种重要的肿瘤转移相关基因的表达调控有关。

Study on Effects of Transducer of ErbB2,1 on Metastasis of Breast Cancer Cell MDA-MB-231 in vitro

Objective To investigate the effects and mechanisms of anti-proliferative protein family number-transducer of erbB2,1（TOB1） on breast cancer cell MDA-MB-231 metastasis.Methods The lipofectamine transfection and selective G418 cell culture were performed to obtain invasive breast cancer cell line MDA-MB-231,which over-expressed TOB1 protein.The effects on breast cancer cell invasion and migration in vitro were evaluated by basal membrane invasion assay and wound healing assay.Different expression of metastatic genes was evaluated via super array pathway-specific microarray.Results Compared with the control group,increased TOB1 expression significantly suppressed the invasion of MDA-MB-231（P〈0.05）,and repressed MDA-MB-231 migration in vitro.Exogenous TOB1 up-regulated the expression of metastasis suppress gene BRMS1,while suppressed the mRNA expression of metastasis gene HSP90、FXYD5、RHOC、S100A4 in MDA-MB-231（all P〈0.05）.Conclusion TOB1 over-expression will lead to the invasion and migration suppression of MDA-MB-231 in vitro,possibly by regulating the expression of metastasis related genes.