COX-2 activation is associated with Akt phosphorylation and poor survival in ER-negative, HER2-positive breast cancer

Abstract

Inducible cyclooxgenase-2 (COX-2) is commonly overexpressed in breast tumors and is a target for cancer therapy. Here, we studied the association of COX-2 with breast cancer survival and how this association is influenced by tumor estrogen and HER2 receptor status and Akt pathway activation. Tumor COX-2, HER2 and estrogen receptor α (ER) expression and phosphorylation of Akt, BAD, and caspase-9 were analyzed immunohistochemically in 248 cases of breast cancer. Spearman's correlation and multivariable logistic regression analyses were used to examine the relationship between COX-2 and tumor characteristics. Kaplan-Meier survival and multivariable Cox proportional hazards regression analyses were used to examine the relationship between COX-2 and disease-specific survival. COX-2 was significantly associated with breast cancer outcome in ER-negative [Hazard ratio (HR) = 2.72; 95% confidence interval (CI), 1.36-5.41; comparing high versus low COX-2] and HER2 overexpressing breast cancer (HR = 2.84; 95% CI, 1.07-7.52). However, the hazard of poor survival associated with increased COX-2 was highest among patients who were both ER-negative and HER2-positive (HR = 5.95; 95% CI, 1.01-34.9). Notably, COX-2 expression in the ER-negative and HER2-positive tumors correlated significantly with increased phosphorylation of Akt and of the two Akt targets, BAD at Ser136 and caspase-9 at Ser196. Up-regulation of COX-2 in ER-negative and HER2-positive breast tumors is associated with Akt pathway activation and is a marker of poor outcome. The findings suggest that COX-2-specific inhibitors and inhibitors of the Akt pathway may act synergistically as anticancer drugs in the ER-negative and HER2-positive breast cancer subtype.

DOI: 10.1186/1471-2407-10-626

Extracted Key Phrases

9 Figures and Tables

0502011201220132014201520162017
Citations per Year

185 Citations

Semantic Scholar estimates that this publication has 185 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@inproceedings{Glynn2010COX2AI, title={COX-2 activation is associated with Akt phosphorylation and poor survival in ER-negative, HER2-positive breast cancer}, author={Sharon A. Glynn and Robyn L. Prueitt and Lisa A. Ridnour and Brenda J. Boersma and Tiffany M Dorsey and David Anderson Wink and Julie E. Goodman and Harris G. Yfantis and Dong Hoon Lee and Stefan Ambs}, booktitle={BMC Cancer}, year={2010} }