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

Mol Cancer. 2010 Oct 13:9:272. doi: 10.1186/1476-4598-9-272.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / physiology
  • Blotting, Western
  • Caspase 3
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Genetic Vectors / genetics
  • Humans
  • Immunohistochemistry
  • Lentivirus / genetics
  • Membrane Potential, Mitochondrial / genetics
  • Membrane Potential, Mitochondrial / physiology
  • Mice
  • Mice, SCID
  • Ovarian Neoplasms / enzymology*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / therapy
  • Reverse Transcriptase Polymerase Chain Reaction
  • Xenograft Model Antitumor Assays
  • ran GTP-Binding Protein / genetics
  • ran GTP-Binding Protein / metabolism*

Substances

  • Caspase 3
  • ran GTP-Binding Protein