An essential role for Ran GTPase in epithelial ovarian cancer cell survival

作者:Barres Veronique; Ouellet Veronique; Lafontaine Julie; Tonin Patricia N; Provencher Diane M; Mes Masson Anne Marie*
来源:Molecular Cancer, 2010, 9(1): 272.
DOI:10.1186/1476-4598-9-272

摘要

Background: 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. Results: 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. Conclusion: 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.

  • 出版日期2010-10-13