Skip Navigation



Carcinogenesis Advance Access published online on December 6, 2005
Carcinogenesis, doi:10.1093/carcin/bgi289
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
27/4/729    most recent
bgi289v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by McPhillips, F.
Right arrow Articles by Langdon, S. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McPhillips, F.
Right arrow Articles by Langdon, S. P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received July 29, 2005
Revised November 20, 2005
Accepted November 22, 2005

CANCER BIOLOGY

Raf-1 is the predominant Raf isoform that mediates growth factor-stimulated growth in ovarian cancer cells

Fiona McPhillips 1, Peter Mullen 1, Kenneth G. MacLeod 1, Jane M. Sewell 1, Brett P. Monia 2, David A. Cameron 1, John F. Smyth 1, and Simon P. Langdon 1 *

1 Cancer Research UK Centre, University of Edinburgh, Edinburgh, EH4 2XR, UK
2 Isis Pharmaceuticals Inc., Carlsbad, CA, 92008, USA

* To whom correspondence should be addressed.
Simon P. Langdon, E-mail: simon.langdon{at}cancer.org.uk


  Abstract

There is currently much interest in the role of the Raf family in cancer, particularly since mutated B-Raf has been shown to be oncogenic in certain disease types. In this study we have explored the expression, signaling and function of the three known Raf isoforms (Raf-1, A-Raf and B-Raf) in patients with ovarian cancer. Whereas increased expression of Raf-1 was associated with poor survival, increased expression of B-Raf was associated with improved survival. Using a panel of ovarian cancer cell lines, all 3 isoforms were shown to be involved in growth factor initiated signaling. Antisense inhibition of function in ovarian cancer cell lines indicated that both Raf-1 and A-Raf, but not B-Raf, were linked to cell proliferation. Raf-1 (but not A-Raf or B-Raf) was also associated with reduced apoptosis. While individual Raf reduction by isoform-targeted antisense oligonucleotides (ODN's) produced growth inhibition in some cell lines, similar use of the MEK inhibitor UO126 produced growth inhibition in all cell lines tested. These data suggest that Raf-1 is the predominant Raf isoform responsible for regulating cellular growth in ovarian cancer cells and may be particularly important in high grade serous ovarian cancers.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 CarcinogenesisHome page
F. Fan, L. Feng, J. He, X. Wang, X. Jiang, Y. Zhang, Z. Wang, and Y. Chen
RKTG sequesters B-Raf to the Golgi apparatus and inhibits the proliferation and tumorigenicity of human malignant melanoma cells
Carcinogenesis, June 1, 2008; 29(6): 1157 - 1163.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.