Normal breast epithelial cells induce apoptosis of breast cancer cells via Fas signaling

Experimental Cell Research
Robert-Alain ToillonXuefen Le Bourhis

Abstract

Fas/Fas ligand (Fas L) death pathway is an important mediator of apoptosis. Deregulation of Fas pathway is reported to be involved in the immune escape of breast cancer and the resistance to anti-cancer drugs. In this study, we demonstrated that conditioned medium by normal breast epithelial cells (NBEC-CM) induced apoptosis of MCF-7 and T-47D Fas-sensitive cells but had no effect on MDA-MB-231 Fas-resistant cells. Inhibition of PI3 kinase or NF-kappaB by specific inhibitors or transient transfections restored the sensitivity of MDA-MB-231 cells to NBEC-induced apoptosis. Moreover, the constitutive activation of NF-kappaB was controlled by PI3 kinase because inhibition of PI3 kinase reduced NF-kappaB activity. Inducible activation of NF-kappaB rendered MCF-7 cells resistant to NBEC-CM- and Fas agonist antibody-triggered apoptosis. Therefore, constitutive or inducible activation of PI3 kinase and/or NF-kappaB in breast cancer cells rendered them resistant to NBEC-triggered apoptosis. In addition, Fas neutralizing antibody and dominant negative Fas abolished NBEC-triggered apoptosis. Western blot and confocal microscopy analysis showed an increase of membrane Fas/Fas L when cells were induced into apoptotis by NBEC-CM. Taken toge...Continue Reading

Citations

Oct 13, 2006·The Journal of Alternative and Complementary Medicine : Research on Paradigm, Practice, and Policy·Grace G L YueClara B S Lau
Apr 11, 2009·International Journal of Oncology·Sateesh KunigalJasti S Rao
Mar 26, 2010·Cellular & Molecular Biology Letters·Vesna BucanPeter M Vogt
Mar 6, 2007·International Journal of Radiation Oncology, Biology, Physics·Robert-Alain ToillonMarc Lacroix
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Nov 14, 2002·Current Problems in Cancer·Harikrishna Nakshatri, Robert J Goulet

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