Neuropeptide-inducible upregulation of proteasome activity precedes nuclear factor kappa B activation in androgen-independent prostate cancer cells.

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Version: author
Serval ID
serval:BIB_3387D467F9F8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Neuropeptide-inducible upregulation of proteasome activity precedes nuclear factor kappa B activation in androgen-independent prostate cancer cells.
Journal
Cancer Cell International
Author(s)
Patrikidou A., Vlachostergios P.J., Voutsadakis I.A., Hatzidaki E., Valeri R.M., Destouni C., Apostolou E., Papandreou C.N.
ISSN
1475-2867 (Electronic)
ISSN-L
1475-2867
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
12
Number
1
Pages
31
Language
english
Notes
Publication types: Journal Article
Abstract
ABSTRACT:
BACKGROUND: Upregulation of nuclear factor kappa B (NFκB) activity and neuroendocrine differentiation are two mechanisms known to be involved in prostate cancer (PC) progression to castration resistance. We have observed that major components of these pathways, including NFκB, proteasome, neutral endopeptidase (NEP) and endothelin 1 (ET-1), exhibit an inverse and mirror image pattern in androgen-dependent (AD) and -independent (AI) states in vitro.
METHODS: We have now investigated for evidence of a direct mechanistic connection between these pathways with the use of immunocytochemistry (ICC), western blot analysis, electrophoretic mobility shift assay (EMSA) and proteasome activity assessment.
RESULTS: Neuropeptide (NP) stimulation induced nuclear translocation of NFκB in a dose-dependent manner in AI cells, also evident as reduced total inhibitor κB (IκB) levels and increased DNA binding in EMSA. These effects were preceded by increased 20 S proteasome activity at lower doses and at earlier times and were at least partially reversed under conditions of NP deprivation induced by specific NP receptor inhibitors, as well as NFκB, IκB kinase (IKK) and proteasome inhibitors. AD cells showed no appreciable nuclear translocation upon NP stimulation, with less intense DNA binding signal on EMSA.
CONCLUSIONS: Our results support evidence for a direct mechanistic connection between the NPs and NFκB/proteasome signaling pathways, with a distinct NP-induced profile in the more aggressive AI cancer state.
Pubmed
Web of science
Open Access
Yes
Create date
11/10/2012 16:54
Last modification date
20/08/2019 13:19
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