Abstract
INTRODUCTION: Nuclear factor-kappaB pathway (NF-kappaB) is activated in many breast cancers. NF-small kappaB has interactions with other pathways such as the nerve growth factor (NGF) pathway, which is involved in the survival and proliferation of breast cancer cells. NGF treatment of breast cancer cells activates NF-kappaB resulting in the inhibition of ceramide-induced apoptosis. NGF effects on apoptosis and cell proliferation are mediated through p75NTR and p140TrkA receptors, respectively. In this study we investigate the NGF/NF-kappaB pathway as a therapeutic target in breast cancer. RESULTS: We demonstrate that p75NTR inhibitor Pep5, p140TrkA inhibitor K-252a, and NF-kappaB inhibitor BAY11-7085 have pro-apoptotic and anti-proliferation activities in breast cancer cells. We also show a synergy in combining the NGF receptor inhibitors with the conventional breast cancer treatments tamoxifen and taxol. CONCLUSION: These data suggest that NGF/NF-kappaB pathway is a potential therapeutic target in breast cancer.