Skip to main content
Erschienen in: Journal of Cancer Research and Clinical Oncology 2/2009

01.02.2009 | Original Paper

Nerve growth factor/nuclear factor-κB pathway as a therapeutic target in breast cancer

verfasst von: Ali Naderi, Luke Hughes-Davies

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 2/2009

Einloggen, um Zugang zu erhalten

Abstract

Introduction

Nuclear factor-κB pathway (NF-κB) is activated in many breast cancers. NF-кB 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-κB 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-κB pathway as a therapeutic target in breast cancer.

Results

We demonstrate that p75NTR inhibitor Pep5, p140TrkA inhibitor K-252a, and NF-κB 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-κB pathway is a potential therapeutic target in breast cancer.
Literatur
Zurück zum Zitat de Graffenried LA, Chandrasekar B, Friedrichs WE et al (2004) NF-kappa B inhibition markedly enhances sensitivity of resistant breast cancer tumor cells to tamoxifen. Ann Oncol 15(6):885–890CrossRef de Graffenried LA, Chandrasekar B, Friedrichs WE et al (2004) NF-kappa B inhibition markedly enhances sensitivity of resistant breast cancer tumor cells to tamoxifen. Ann Oncol 15(6):885–890CrossRef
Zurück zum Zitat Descamps S, Toillon RA, Adriaenssens E et al (2001) Nerve growth factor stimulates proliferation and survival of human breast cancer cells through two distinct signalling pathways. J Biol Chem 276(21):17864–17870PubMedCrossRef Descamps S, Toillon RA, Adriaenssens E et al (2001) Nerve growth factor stimulates proliferation and survival of human breast cancer cells through two distinct signalling pathways. J Biol Chem 276(21):17864–17870PubMedCrossRef
Zurück zum Zitat Dolle L, Adriaenssens E, El Yazidi-Belkoura I et al (2004) Nerve growth factor receptors and signaling in breast cancer. Curr Cancer Drug Targets 4(6):463–470PubMedCrossRef Dolle L, Adriaenssens E, El Yazidi-Belkoura I et al (2004) Nerve growth factor receptors and signaling in breast cancer. Curr Cancer Drug Targets 4(6):463–470PubMedCrossRef
Zurück zum Zitat Dolle L, Oliveira MJ, Bruyneel E et al (2005) Nerve growth factor mediates its pro-invasive effect in parallel with the release of a soluble E-cadherin fragment from breast cancer MCF-7/AZ cells. J Dairy Res 72 Spec No:20–26PubMedCrossRef Dolle L, Oliveira MJ, Bruyneel E et al (2005) Nerve growth factor mediates its pro-invasive effect in parallel with the release of a soluble E-cadherin fragment from breast cancer MCF-7/AZ cells. J Dairy Res 72 Spec No:20–26PubMedCrossRef
Zurück zum Zitat El Yazidi-Belkoura I, Adriaenssens E, Dolle L et al (2003) Tumor necrosis factor receptor-associated death domain protein is involved in the neurotrophin receptor-mediated antiapoptotic activity of nerve growth factor in breast cancer cells. J Biol Chem 278(19):16952–16956PubMedCrossRef El Yazidi-Belkoura I, Adriaenssens E, Dolle L et al (2003) Tumor necrosis factor receptor-associated death domain protein is involved in the neurotrophin receptor-mediated antiapoptotic activity of nerve growth factor in breast cancer cells. J Biol Chem 278(19):16952–16956PubMedCrossRef
Zurück zum Zitat Naderi A, Teschendorff AE, Beigel J et al (2007) BEX2 is overexpressed in a subset of primary breast cancers and mediates nerve growth factor/nuclear factor-kappaB inhibition of apoptosis in breast cancer cell lines. Cancer Res 67(14):6725–6736PubMedCrossRef Naderi A, Teschendorff AE, Beigel J et al (2007) BEX2 is overexpressed in a subset of primary breast cancers and mediates nerve growth factor/nuclear factor-kappaB inhibition of apoptosis in breast cancer cell lines. Cancer Res 67(14):6725–6736PubMedCrossRef
Zurück zum Zitat Oh I, Ozaki K, Sato K et al (2007) Interferon-gamma and NF-kappaB mediate nitric oxide production by mesenchymal stromal cells. Biochem Biophys Res Commun 335(4):956–962CrossRef Oh I, Ozaki K, Sato K et al (2007) Interferon-gamma and NF-kappaB mediate nitric oxide production by mesenchymal stromal cells. Biochem Biophys Res Commun 335(4):956–962CrossRef
Zurück zum Zitat Pratt MA, Bishop TE, White D et al (2003) Estrogen withdrawal-induced NF-kappaB activity and bcl-3 expression in breast cancer cells: roles in growth and hormone independence. Mol Cell Biol 19:6887–6900CrossRef Pratt MA, Bishop TE, White D et al (2003) Estrogen withdrawal-induced NF-kappaB activity and bcl-3 expression in breast cancer cells: roles in growth and hormone independence. Mol Cell Biol 19:6887–6900CrossRef
Zurück zum Zitat Reddel RR, Sutherland RL (1984) Tamoxifen stimulation of human breast cancer cell proliferation in vitro: a possible model for tamoxifen tumour flare. Euro J Cancer Clin Oncol 20(11):1419–1424CrossRef Reddel RR, Sutherland RL (1984) Tamoxifen stimulation of human breast cancer cell proliferation in vitro: a possible model for tamoxifen tumour flare. Euro J Cancer Clin Oncol 20(11):1419–1424CrossRef
Zurück zum Zitat Riggins RB, Zwart A, Nehra R et al (2005) The nuclear factor kappa B inhibitor parthenolide restores ICI 182, 780 (Faslodex; fulvestrant)-induced apoptosis in antiestrogen-resistant breast cancer cells. Mol Cancer Ther 4(1):33–41PubMed Riggins RB, Zwart A, Nehra R et al (2005) The nuclear factor kappa B inhibitor parthenolide restores ICI 182, 780 (Faslodex; fulvestrant)-induced apoptosis in antiestrogen-resistant breast cancer cells. Mol Cancer Ther 4(1):33–41PubMed
Zurück zum Zitat Singh S, Shi Q, Bailey ST et al (2007) Nuclear factor-B activation: a molecular therapeutic target for estrogen receptor–negative and epidermal growth factor receptor family receptor–positive human breast cancer. Mol Cancer Ther 6(7):1973–1982PubMedCrossRef Singh S, Shi Q, Bailey ST et al (2007) Nuclear factor-B activation: a molecular therapeutic target for estrogen receptor–negative and epidermal growth factor receptor family receptor–positive human breast cancer. Mol Cancer Ther 6(7):1973–1982PubMedCrossRef
Zurück zum Zitat Yamashita T, Tohyama M (2003) The p75 receptor acts as a displacement factor that releases Rho from Rho-GDI. Nat Neurosci 6(5):461–467PubMed Yamashita T, Tohyama M (2003) The p75 receptor acts as a displacement factor that releases Rho from Rho-GDI. Nat Neurosci 6(5):461–467PubMed
Metadaten
Titel
Nerve growth factor/nuclear factor-κB pathway as a therapeutic target in breast cancer
verfasst von
Ali Naderi
Luke Hughes-Davies
Publikationsdatum
01.02.2009
Verlag
Springer-Verlag
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 2/2009
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-008-0455-6

Weitere Artikel der Ausgabe 2/2009

Journal of Cancer Research and Clinical Oncology 2/2009 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.