An essential role for Ran GTPase in epithelial ovarian cancer cell survival.
An essential role for Ran GTPase in epithelial ovarian cancer cell survival.
复制标题
DOI：
10.1186/1476-4598-9-272
复制
发表时间：
2010-10-13
期刊：
影响因子：
37.3
通讯作者：
Mes-Masson AM
中科院分区：
文献类型：
--
作者：
Barrès V;Ouellet V;Lafontaine J;Tonin PN;Provencher DM;Mes-Masson AM
我们之前发现Ran蛋白是Ras GTPase家族的成员，在高级别和高阶段浆液性上皮性卵巢癌中高表达，并且其过度表达与不良预后相关。已知 Ran 有助于核细胞质运输和细胞周期进展，但其在卵巢癌中的作用尚不清楚。使用基于慢病毒的四环素诱导 shRNA 方法，我们发现侵袭性卵巢癌细胞系中 Ran 表达的下调通过诱导 caspase-3 相关的细胞凋亡来影响细胞增殖。使用异种移植肿瘤测定，我们证明 Ran 的消耗会导致肿瘤发生减少，并且最终的肿瘤形成与表达 Ran 蛋白的肿瘤细胞有关。我们的结果表明 Ran 在卵巢癌细胞存活和致瘤性中发挥作用，并表明这种关键的 GTPase 可能适合作为治疗靶点。
We previously identified that Ran protein, a member of the Ras GTPase family, is highly expressed in high grade and high stage serous epithelial ovarian cancers, and that its overexpression is associated with a poor prognosis. Ran is known to contribute to both nucleocytoplasmic transport and cell cycle progression, but its role in ovarian cancer is not well defined. Using a lentivirus-based tetracycline-inducible shRNA approach, we show that downregulation of Ran expression in aggressive ovarian cancer cell lines affects cellular proliferation by inducing a caspase-3 associated apoptosis. Using a xenograft tumor assay, we demonstrate that depletion of Ran results in decreased tumorigenesis, and eventual tumor formation is associated with tumor cells that express Ran protein. Our results suggest a role for Ran in ovarian cancer cell survival and tumorigenicity and suggest that this critical GTPase may be suitable as a therapeutic target.
登录
查看更多内容
影响因子：
6.4
作者：
Abe, Hideyuki;Kamai, Takao;Yoshida, Ken-ichiro
通讯作者：
Yoshida, Ken-ichiro
影响因子：
3.7
作者：
Li, Hui;Ren, Cai-Ping;Yao, Kai-Tai
通讯作者：
Yao, Kai-Tai
影响因子：
3.1
作者：
Chung, SW;Huang, XY;Wong, PMC
通讯作者：
Wong, PMC
影响因子：
11.5
作者：
Azuma, K;Sasada, T;Itoh, K
通讯作者：
Itoh, K
影响因子：
2.4
作者：
Levi, F;Lucchini, F;La Vecchia, C
通讯作者：
La Vecchia, C