The possibility of WT1 gene for new therapeutic target in ovarian cancer

在这项研究中，我们试图在体内卵巢癌模型中研究WT1剪接变异体对致瘤活性和生存的影响。腹腔接种表达WT1 -17AA/-KTS的SKOV3ip1细胞的小鼠，与接种表达对照载体的小鼠相比，弥散性肿瘤重量和腹水产量显著增加。表达WT1 -17AA/- kts细胞的小鼠总体生存期明显短于对照组。与对照组相比，WT1 -17AA/-KTS显著增加了血管内皮生长因子（VEGF）的表达和肿瘤微血管密度。这些结果表明，WT1 -17AA/-KTS可通过上调卵巢癌中VEGF的表达而增强肿瘤活性，降低患者生存期。WT1 -17AA/-KTS的表达可能诱导卵巢癌细胞进入更具侵袭性的表型。

In this study, we sought to investigate the effects of WT1 splice variants on tumorigenic activity and survival in an in vivo ovarian cancer model. In mice inoculated intraperitoneally with SKOV3ip1 cells expressing WT1 -17AA/-KTS, disseminated tumor weights and production of ascites were significantly increased compared with those in mice inoculated with cells expressing the control vector. The overall survival in mice with WT1 -17AA/-KTS-expressing cells was significantly shorter than that in mice with control cells. WT1 -17AA/-KTS significantly increased the expression of vascular endothelial growth factor (VEGF) and tumor microvessel density compared with the control. These results indicated that WT1 -17AA/-KTS could enhance tumorigenic activity and could decrease patient survival through up-regulation of VEGF expression in ovarian cancers. The expression of WT1 -17AA/-KTS may induce ovarian cancer cells into a more aggressive phenotype.