Teoh Sonia S Y, Vieusseux Jessica, Prakash Monica, Berkowicz Susan, Luu Jennii, Bird Catherina H, Law Ruby H P, Rosado Carlos, Price John T, Whisstock James C, Bird Phillip I
Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Victoria 3800, Australia.
1] Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Victoria 3800, Australia [2] Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, School of Biomedical Sciences, Monash University, Victoria 3800, Australia.
Nat Commun. 2014;5:3164. doi: 10.1038/ncomms4164.
Maspin (SERPINB5) is accepted as an important tumour suppressor lost in many cancers. Consistent with a critical role in development or differentiation maspin knockout mice die during early embryogenesis, yet clinical data conflict on the prognostic utility of maspin expression. Here to reconcile these findings we made conditional knockout mice. Surprisingly, maspin knockout embryos develop into overtly normal animals. Contrary to original reports, maspin re-expression does not inhibit tumour growth or metastasis in vivo, or influence cell migration, invasion or survival in vitro. Bioinformatic analyses reveal that maspin is not commonly under-expressed in cancer, and that perturbation of genes near maspin may in fact explain poor survival in certain patient cohorts with low maspin expression.
Maspin(丝氨酸蛋白酶抑制剂B5)被认为是一种在多种癌症中缺失的重要肿瘤抑制因子。与在发育或分化中起关键作用一致,maspin基因敲除小鼠在胚胎早期发育过程中死亡,但关于maspin表达的预后效用,临床数据存在矛盾。在此,为了调和这些发现,我们制作了条件性基因敲除小鼠。令人惊讶的是,maspin基因敲除胚胎发育成外观正常的动物。与最初的报道相反,maspin的重新表达在体内并不抑制肿瘤生长或转移,在体外也不影响细胞迁移、侵袭或存活。生物信息学分析表明,maspin在癌症中并不常见低表达,实际上maspin附近基因的扰动可能解释了某些maspin低表达患者队列的不良生存情况。