Association of c-Raf expression with survival and its targeting with antisense oligonucleotides in ovarian cancer

F McPhillips, P Mullen, B P Monia, A A Ritchie, F A Dorr, J F Smyth, S P Langdon

Research output: Contribution to journalArticlepeer-review


c-Raf is an essential component of the extracellular related kinase (ERK) signal transduction pathway. Immunohistochemical staining indicated that c-Raf was present in 49/53 ovarian adenocarcinomas investigated and high c-Raf expression correlated significantly with poor survival (P = 0.002). c-Raf protein was detected in 15 ovarian cancer cell lines. Antisense oligodeoxynucleotides (ODNs) (ISIS 5132 and ISIS 13650) reduced c-Raf protein levels and inhibited cell proliferation in vitro. Selectivity was demonstrated by the lack of effect of ISIS 5132 on A-Raf or ERK, while a random ODN produced only minor effects on growth and did not influence c-Raf expression. ISIS 5132 produced enhanced apoptosis and cells accumulated in S and G(2)/M phases of the cell cycle. In vivo, ISIS 5132 inhibited growth of the s.c. SKOV-3 xenograft while a mismatch ODN had no effect. These data indicate that high levels of c-Raf expression may be important in ovarian cancer and use of antisense ODNs targeted to c-Raf could provide a strategy for the treatment of this disease.

Original languageEnglish
Pages (from-to)1753-8
Number of pages6
JournalBritish Journal of Cancer
Issue number11
Publication statusPublished - 30 Nov 2001


  • Animals
  • Cell Cycle/drug effects
  • Cell Division/drug effects
  • DNA, Antisense/pharmacology
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Ovarian Neoplasms/drug therapy
  • Proto-Oncogene Proteins c-raf/biosynthesis
  • Survival Analysis
  • Time Factors
  • Xenograft Model Antitumor Assays


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