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

Véronique Barrès1, Véronique Ouellet1, Julie Lafontaine1, Patricia N Tonin234, Diane M Provencher156 and Anne-Marie Mes-Masson16*

Author Affiliations

1 Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM)/Institut du cancer de Montréal,1560 Sherbrooke Est, Montreal, H2L 4M1, Canada

2 Department of Medicine, McGill University, Montreal, Canada

3 Department of Human Genetics, McGill University, Montreal, Canada

4 Research Institute of McGill University Health Centre (RI-MUHC), 1650 Cedar Avenue, Montreal, H3G 1A4, Quebec, Canada

5 Department of Obstetric-Gynecology/Université de Montréal, Montreal, Canada

6 Départment of Medecine, Université de Montréal, Montreal, Canada

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Molecular Cancer 2010, 9:272  doi:10.1186/1476-4598-9-272

Published: 13 October 2010

Abstract

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.