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Inflammatory cytokines and survival factors from serum modulate tweak-induced apoptosis in PC-3 Prostate Cancer Cells

Author
Sanz, Ana Belén; Sánchez-Niño, María Dolores; Carrasco, Susana; Manzarbeitia, Félix; Ruíz Andrés, Olga; Selgas, Rafael; Ruíz-Ortega, Marta; González-Enguita, Carmen; Egido, Jesús; Ortíz, Alberto
Entity
UAM. Departamento de Medicina
Publisher
Public Library of Science
Date
2012-10-15
Citation
10.1371/journal.pone.0047440
PLoS one 7.10 (2012): e47440
 
 
 
ISSN
1932-6203 (online)
DOI
10.1371/journal.pone.0047440
Funded by
Grant support from Fondo de Investigacion Sanitaria (FIS) PS09/00447, Instituto de Salud Carlos III-Redes Temáticas de Investigación Cooperativa en Salud(ISCIII-RETIC)REDinREN/RD06/0016.
Project
Comunidad de Madrid. S2010/BMD-2378/CIFRA
Editor's Version
http://dx.doi.org/10.1371/journal.pone.0047440
Subjects
Apoptosis; Cell stainig; Cytokines; Flow cytometry; Inflammation; Necrotic cell death; Prostate cancer; Prostate gland; Medicina
URI
http://hdl.handle.net/10486/660692
Rights
© 2012 Sanz et al.

Abstract

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK, TNFSF12) is a member of the tumor necrosis factor superfamily. TWEAK activates the Fn14 receptor, and may regulate cell death, survival and proliferation in tumor cells. However, there is little information on the function and regulation of this system in prostate cancer. Fn14 expression and TWEAK actions were studied in two human prostate cancer cell lines, the androgen-independent PC-3 cell line and androgen-sensitive LNCaP cells. Additionally, the expression of Fn14 was analyzed in human biopsies of prostate cancer. Fn14 expression is increased in histological sections of human prostate adenocarcinoma. Both prostate cancer cell lines express constitutively Fn14, but, the androgen-independent cell line PC-3 showed higher levels of Fn14 that the LNCaP cells. Fn14 expression was up-regulated in PC-3 human prostate cancer cells in presence of inflammatory cytokines (TNFa/IFNc) as well as in presence of bovine fetal serum. TWEAK induced apoptotic cell death in PC-3 cells, but not in LNCaP cells. Moreover, in PC-3 cells, co-stimulation with TNFa/IFNc/TWEAK induced a higher rate of apoptosis. However, TWEAK or TWEAK/TNFa/IFNc did not induce apoptosis in presence of bovine fetal serum. TWEAK induced cell death through activation of the Fn14 receptor. Apoptosis was associated with activation of caspase-3, release of mitochondrial cytochrome C and an increased Bax/BclxL ratio. TWEAK/Fn14 pathway activation promotes apoptosis in androgen-independent PC-3 cells under certain culture conditions. Further characterization of the therapeutic target potential of TWEAK/Fn14 for human prostate cancer is warranted.
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Google™ Scholar:Sanz, Ana Belén - Sánchez-Niño, María Dolores - Carrasco, Susana - Manzarbeitia, Félix - Ruíz Andrés, Olga - Selgas, Rafael - Ruíz-Ortega, Marta - González-Enguita, Carmen - Egido, Jesús - Ortíz, Alberto

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  • Producción científica en acceso abierto de la UAM [14403]

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All the documents from Biblos-e Archivo are protected by copyrights. Some rights reserved.
Universidad Autónoma de Madrid. Biblioteca
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