Skip to main content
main-content

01.12.2012 | Primary research | Ausgabe 1/2012 Open Access

Cancer Cell International 1/2012

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

Zeitschrift:
Cancer Cell International > Ausgabe 1/2012
Autoren:
Anna Patrikidou, Panagiotis J Vlachostergios, Ioannis A Voutsadakis, Eleana Hatzidaki, Rosalia-Maria Valeri, Chariklia Destouni, Effie Apostolou, Christos N Papandreou
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1475-2867-12-31) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

CNP and AP designed the study. EH, RMV, CD and EA performed experiments. AP and PJV drafted the manuscript. PJV, IAV and CNP revised the manuscript. All authors read and approved the final manuscript.

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.
Zusatzmaterial
Authors’ original file for figure 1
12935_2012_347_MOESM1_ESM.tiff
Authors’ original file for figure 2
12935_2012_347_MOESM2_ESM.tiff
Authors’ original file for figure 3
12935_2012_347_MOESM3_ESM.tiff
Authors’ original file for figure 4
12935_2012_347_MOESM4_ESM.tiff
Authors’ original file for figure 5
12935_2012_347_MOESM5_ESM.tiff
Authors’ original file for figure 6
12935_2012_347_MOESM6_ESM.tiff
Authors’ original file for figure 7
12935_2012_347_MOESM7_ESM.tiff
Authors’ original file for figure 8
12935_2012_347_MOESM8_ESM.tiff
Authors’ original file for figure 9
12935_2012_347_MOESM9_ESM.tiff
Authors’ original file for figure 10
12935_2012_347_MOESM10_ESM.tiff
Authors’ original file for figure 11
12935_2012_347_MOESM11_ESM.tiff
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 1/2012

Cancer Cell International 1/2012 Zur Ausgabe