Centre de Recherche du Centre Hospitalier de l'Université de Montréal/Institut du cancer de Montréal,1560 Sherbrooke Est, Montreal H2L 4M1, Canada.
Mol Cancer. 2010 Oct 13;9:272. doi: 10.1186/1476-4598-9-272.
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.
我们之前发现，Ran 蛋白是 Ras GTPase 家族的一员，在高级别和高分期的浆液性上皮性卵巢癌中高度表达，其过表达与预后不良相关。Ran 已知既参与核质转运又参与细胞周期进程，但它在卵巢癌中的作用尚未明确。
我们使用基于慢病毒的四环素诱导性 shRNA 方法，证明在侵袭性卵巢癌细胞系中下调 Ran 表达通过诱导 caspase-3 相关的凋亡来影响细胞增殖。通过异种移植肿瘤测定，我们证明 Ran 的耗竭会导致肿瘤发生减少，最终肿瘤形成与表达 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起作用，并表明该关键 GTPase 可能适合作为治疗靶标。
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