title: Inverse baseline expression pattern of the NEP/neuropeptides and NFκB/proteasome pathways in androgen-dependent and androgen-independent prostate cancer cells.
abstract: BACKGROUND
  Castration-resistance in prostate cancer (PC) is a critical event hallmarking a switch to a more aggressive phenotype. Neuroendocrine differentiation and upregulation of NFκB transcriptional activity are two mechanisms that have been independently linked to this process.
  
  
  METHODS
  We investigated these two pathways together using in vitro models of androgen-dependent (AD) and androgen-independent (AI) PC. We measured cellular levels, activity and surface expression of Neutral Endopeptidase (NEP), levels of secreted Endothelin-1 (ET-1), levels, sub-cellular localisation and DNA binding ability of NFκB, and proteasomal activity in human native PC cell lines (LnCaP and PC-3) modelling AD and AI states.
  
  
  RESULTS
  At baseline, AD cells were found to have high NEP expression and activity and low secreted ET-1. In contrast, they exhibited a low-level activation of the NFκB pathway associated with comparatively low 20S proteasome activity. The AI cells showed the exact mirror image, namely increased proteasomal activity resulting in a canonical pathway-mediated NFκB activation, and minimal NEP activity with increased levels of secreted ET-1.
  
  
  CONCLUSIONS
  Our results seem to support evidence for divergent patterns of expression of the NFκB/proteasome pathway with relation to components of the NEP/neuropeptide axis in PC cells of different level of androgen dependence. NEP and ET-1 are inversely and directly related to an activated state of the NFκB/proteasome pathway, respectively. A combination therapy targeting both pathways may ultimately prove to be of benefit in clinical practice.
authors.affiliation: Department of Medical Oncology, University Hospital of Larissa, Larissa, Greece. cpapandreou@med.uth.gr.
authors.forename: Anna
authors.initials: A
authors.lastname: Patrikidou
authors.forename: Panagiotis J
authors.initials: PJ
authors.lastname: Vlachostergios
authors.forename: Ioannis A
authors.initials: IA
authors.lastname: Voutsadakis
authors.forename: Eleana
authors.initials: E
authors.lastname: Hatzidaki
authors.forename: Rosalia-Maria
authors.initials: RM
authors.lastname: Valeri
authors.forename: Chariklia
authors.initials: C
authors.lastname: Destouni
authors.forename: Effie
authors.initials: E
authors.lastname: Apostolou
authors.forename: Danai
authors.initials: D
authors.lastname: Daliani
authors.forename: Christos N
authors.initials: CN
authors.lastname: Papandreou