Coexpression of NOS2 and COX2 accelerates tumor growth and reduces survival in estrogen receptor-negative breast cancer

著者: Debashree Basudhar, Sharon A. Glynn, Madison Greer, Veena Somasundaram, Jae Hong No, David A. Scheiblin, Pablo Garrido, William F. Heinz, Aideen E. Ryan, Jonathan M. Weiss, Robert Y.S. Cheng, Lisa A. Ridnour, Stephen Lockett, Daniel W. McVicar, Stefan Ambs, David A. Wink - Proceedings of the National Academy of Sciences, PNAS 2017 被引用: 119

Significance Nitric oxide synthase-2 (NOS2) and cyclooxygenase-2 (COX2) are inflammation-associated enzymes with oncogenic function in breast cancer. We show that crosstalk between NOS2/COX2 promotes aggressive phenotypes and that elevated coexpression of NOS2/COX2 in tumors predict significantly reduced patient survival (33%) when compared with 95% survival of estrogen receptor-negative patients with low NOS2/COX2 tumor expression. In addition, we have identified a tumor subtype-specific mechanism showing involvement of TNFα and/or endoplasmic reticulum stress as key players in this autocrine loop. Importantly, the simultaneous inhibition of NOS2/COX2 significantly reduced tumor growth in a xenograft murine model, suggesting that targeted inhibition of NOS2/COX2 may be therapeutically beneficial.