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Cancer Cell. 2010 Mar 16;17(3):298-310. doi: 10.1016/j.ccr.2009.12.047.

An activated ErbB3/NRG1 autocrine loop supports in vivo proliferation in ovarian cancer cells.

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  • 1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

Erratum in

  • Cancer Cell. 2010 Apr 13;17(4):412.

Abstract

Ovarian cancer is a leading cause of death from gynecologic malignancies. Treatment for advanced-stage disease remains limited and, to date, targeted therapies have been incompletely explored. By systematically suppressing each human tyrosine kinase in ovarian cancer cell lines by RNAi, we found that an autocrine signal-transducing loop involving NRG1 and activated ErbB3 operates in a subset of primary ovarian cancers and ovarian cancer cell lines. Perturbation of this circuit with ErbB3-directed RNAi decreased cell growth in three-dimensional culture and resulted in decreased disease progression and prolonged survival in a xenograft mouse model of ovarian cancer. Furthermore, a monoclonal ErbB3-directed antibody (MM-121) also significantly inhibited tumor growth in vivo. These findings identify ErbB3 as a potential therapeutic target in ovarian cancer.

Copyright 2010 Elsevier Inc. All rights reserved.

PMID:
20227043
[PubMed - indexed for MEDLINE]
PMCID:
PMC2897158
Free PMC Article
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