Inflammatory cytokines and survival factors from serum modulate tweak-induced apoptosis in PC-3 prostate cancer cells.

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 o...

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Autores principales: Ana Belen Sanz, Maria Dolores Sanchez-Niño, Susana Carrasco, Felix Manzarbeitia, Olga Ruiz-Andres, Rafael Selgas, Marta Ruiz-Ortega, Carmen Gonzalez-Enguita, Jesus Egido, Alberto Ortiz
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Publicado: Public Library of Science (PLoS) 2012
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Acceso en línea:https://doaj.org/article/3861df85a9414a9ca42bb53df64d8938
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spelling oai:doaj.org-article:3861df85a9414a9ca42bb53df64d89382021-11-18T08:11:58ZInflammatory cytokines and survival factors from serum modulate tweak-induced apoptosis in PC-3 prostate cancer cells.1932-620310.1371/journal.pone.0047440https://doaj.org/article/3861df85a9414a9ca42bb53df64d89382012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23077618/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Tumor 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 (TNFα/IFNγ) 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 TNFα/IFNγ/TWEAK induced a higher rate of apoptosis. However, TWEAK or TWEAK/TNFα/IFNγ 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.Ana Belen SanzMaria Dolores Sanchez-NiñoSusana CarrascoFelix ManzarbeitiaOlga Ruiz-AndresRafael SelgasMarta Ruiz-OrtegaMarta Ruiz-OrtegaCarmen Gonzalez-EnguitaJesus EgidoAlberto OrtizPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e47440 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ana Belen Sanz
Maria Dolores Sanchez-Niño
Susana Carrasco
Felix Manzarbeitia
Olga Ruiz-Andres
Rafael Selgas
Marta Ruiz-Ortega
Marta Ruiz-Ortega
Carmen Gonzalez-Enguita
Jesus Egido
Alberto Ortiz
Inflammatory cytokines and survival factors from serum modulate tweak-induced apoptosis in PC-3 prostate cancer cells.
description 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 (TNFα/IFNγ) 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 TNFα/IFNγ/TWEAK induced a higher rate of apoptosis. However, TWEAK or TWEAK/TNFα/IFNγ 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.
format article
author Ana Belen Sanz
Maria Dolores Sanchez-Niño
Susana Carrasco
Felix Manzarbeitia
Olga Ruiz-Andres
Rafael Selgas
Marta Ruiz-Ortega
Marta Ruiz-Ortega
Carmen Gonzalez-Enguita
Jesus Egido
Alberto Ortiz
author_facet Ana Belen Sanz
Maria Dolores Sanchez-Niño
Susana Carrasco
Felix Manzarbeitia
Olga Ruiz-Andres
Rafael Selgas
Marta Ruiz-Ortega
Marta Ruiz-Ortega
Carmen Gonzalez-Enguita
Jesus Egido
Alberto Ortiz
author_sort Ana Belen Sanz
title Inflammatory cytokines and survival factors from serum modulate tweak-induced apoptosis in PC-3 prostate cancer cells.
title_short Inflammatory cytokines and survival factors from serum modulate tweak-induced apoptosis in PC-3 prostate cancer cells.
title_full Inflammatory cytokines and survival factors from serum modulate tweak-induced apoptosis in PC-3 prostate cancer cells.
title_fullStr Inflammatory cytokines and survival factors from serum modulate tweak-induced apoptosis in PC-3 prostate cancer cells.
title_full_unstemmed Inflammatory cytokines and survival factors from serum modulate tweak-induced apoptosis in PC-3 prostate cancer cells.
title_sort inflammatory cytokines and survival factors from serum modulate tweak-induced apoptosis in pc-3 prostate cancer cells.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/3861df85a9414a9ca42bb53df64d8938
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