dc.contributor.author | Basudhar, Debashree | |
dc.contributor.author | Glynn, Sharon A. | |
dc.contributor.author | Greer, Madison | |
dc.contributor.author | Somasundaram, Veena | |
dc.contributor.author | No, Jae Hong | |
dc.contributor.author | Scheiblin, David A. | |
dc.contributor.author | Garrido, Pablo | |
dc.contributor.author | Heinz, William F. | |
dc.contributor.author | Ryan, Aideen E. | |
dc.contributor.author | Weiss, Jonathan M. | |
dc.contributor.author | Cheng, Robert Y. S. | |
dc.contributor.author | Ridnour, Lisa A. | |
dc.contributor.author | Lockett, Stephen J. | |
dc.contributor.author | McVicar, Daniel W. | |
dc.contributor.author | Ambs, Stefan | |
dc.contributor.author | Wink, David A. | |
dc.date.accessioned | 2018-09-20T16:00:41Z | |
dc.date.available | 2018-09-20T16:00:41Z | |
dc.date.issued | 2017-10-27 | |
dc.identifier.citation | Basudhar, Debashree; Glynn, Sharon A. Greer, Madison; Somasundaram, Veena; No, Jae Hong; Scheiblin, David A.; Garrido, Pablo; Heinz, William F.; Ryan, Aideen E.; Weiss, Jonathan M.; Cheng, Robert Y. S.; Ridnour, Lisa A.; Lockett, Stephen J.; McVicar, Daniel W.; Ambs, Stefan; Wink, David A. (2017). Coexpression of nos2 and cox2 accelerates tumor growth and reduces survival in estrogen receptor-negative breast cancer. Proceedings of the National Academy of Sciences 114 (49), 13030-13035 | |
dc.identifier.issn | 0027-8424,1091-6490 | |
dc.identifier.uri | http://hdl.handle.net/10379/10375 | |
dc.description.abstract | Proinflammatory signaling pathways are commonly up-regulated in breast cancer. In estrogen receptor-negative (ER-) and triple-negative breast cancer (TNBC), nitric oxide synthase-2 (NOS2) and cyclooxygenase-2 (COX2) have been described as independent predictors of disease outcome. We further explore these findings by investigating the impact of their coexpression on breast cancer survival. Elevated coexpression of NOS2/COX2 proteins is a strong predictor of poor survival among ER-patients (hazard ratio: 21). Furthermore, we found that the key products of NOS2 and COX2, NO and prostaglandin E2 (PGE2), respectively, promote feed-forward NOS2/COX2 crosstalk in both MDA-MB-468 (basal-like) and MDA-MB-231 (mesenchymal-like) TNBC cell lines in which NO induced COX2 and PGE2 induced NOS2 proteins. COX2 induction by NO involved TRAF2 activation that occurred in a TNF alpha-dependent manner in MDA-MB-468 cells. In contrast, NO-mediated TRAF2 activation in the more aggressive MDA-MB-231 cells was TNF alpha independent but involved the endoplasmic reticulum stress response. Inhibition of NOS2 and COX2 using amino-guanidine and aspirin/indomethacin yielded an additive reduction in the growth of MDAMB-231 tumor xenografts. These findings support a role of NOS2/COX2 crosstalk during disease progression of aggressive cancer phenotypes and offer insight into therapeutic applications for better survival of patients with ER-and TNBC disease. | |
dc.publisher | Proceedings of the National Academy of Sciences | |
dc.relation.ispartof | Proceedings of the National Academy of Sciences | |
dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Ireland | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/3.0/ie/ | |
dc.subject | breast cancer | |
dc.subject | nitric oxide | |
dc.subject | pge2 | |
dc.subject | nos2 | |
dc.subject | cox2 | |
dc.subject | cyclooxygenase-2 expression | |
dc.subject | basal-like | |
dc.subject | inflammation | |
dc.subject | angiogenesis | |
dc.subject | carcinoma | |
dc.subject | tumorigenesis | |
dc.subject | progression | |
dc.subject | metastasis | |
dc.subject | pathways | |
dc.title | Coexpression of nos2 and cox2 accelerates tumor growth and reduces survival in estrogen receptor-negative breast cancer | |
dc.type | Article | |
dc.identifier.doi | 10.1073/pnas.1709119114 | |
dc.local.publishedsource | http://www.pnas.org/content/114/49/13030.full.pdf | |
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