Nerve growth factor/nuclear factor-kappaB pathway as a therapeutic target in breast cancer.
BACKGROUND
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.


CONCLUSIONS
These data suggest that NGF/NF-kappaB pathway is a potential therapeutic target in breast cancer.
Naderi
Ali
A
Diamantina Institute for Cancer, Immunology and Metabolic Medicine, Cancer Biology Program, University of Queensland, Princess Alexandra Hospital, Brisbane, QLD, 4102, Australia. a.naderi@uq.edu.au
Hughes-Davies
Luke
L
D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D016328:NF-kappa B / Q000627:therapeutic use*; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics; D013629:Tamoxifen / Q000627:therapeutic use
D016328:NF-kappa B; D009414:Nerve Growth Factors; D017475:Receptors, Nerve Growth Factor; D013629:Tamoxifen