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. 2001 Nov;85(11):1753–1758. doi: 10.1054/bjoc.2001.2139

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

F McPhillips 1, P Mullen 1, B P Monia 2, A A Ritchie 1, F A Dorr 2, J F Smyth 1, S P Langdon 1
PMCID: PMC2363986  PMID: 11742498

Abstract

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. © 2001 Cancer Research Campaign http://www.bjcancer.com

Keywords: Raf, antisense, ovarian, cancer, oligodeoxynucleotide

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Selected References

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