Document Detail

Regulation of neuroendocrine differentiation by AKT/hnRNPK/AR/β-catenin signaling in prostate cancer cells.
MedLine Citation:
PMID:  22015967     Owner:  NLM     Status:  MEDLINE    
Current diagnostic tools cannot predict clinical failure and androgen-independent disease progression for patients with prostate cancer (PC). The survival signaling pathways of prostate cells play a central role in the progression of tumors to a neuroendocrine (NE) phenotype. NE cells demonstrate attributes that suggest that they are an integral part of the signaling cascade leading to castration-resistant PC. In this study, making use of in vitro neuroendocrine differentiation (NED) of human LNCaP and mouse TRAMP-C2 cells after androgen withdrawal, and of the transgenic adenocarcinoma of mouse prostate (TRAMP) model, we characterized a sequence of molecular events leading to NED and identified a number of markers that could be detectable by routine analyses not only in castration resistant PC but also in hormone naïve PC at the time of initial diagnosis. We found that NED associates with AKT activation that in turn regulates heterogeneous nuclear ribonucleoprotein K (hnRNP K), androgen receptor (AR) and β-catenin levels. Addition of molecules targeting membrane-bound receptors and protein kinases blocks NE differentiation in LNCaP and TRAMP-C2 cells. The extent of AKT phosphorylation and hnRNP K, AR and β-catenin levels may have a potential value as prognostic indicators discriminating between androgen-responsive and unresponsive cells and could be used as molecular targets to monitor the anti-tumor action of new therapeutic protocols based on antireceptor agents and/or neuroendocrine hormone antagonists.
Monica Ciarlo; Roberto Benelli; Ottavia Barbieri; Simona Minghelli; Paola Barboro; Cecilia Balbi; Nicoletta Ferrari
Related Documents :
3084637 - Effect of gamma radiation on resting b lymphocytes. i. oxygen-dependent damage to the p...
1884367 - Effect of oxygenation, ph and hyperthermia on rsu-1069 in vitro and in vivo with radiat...
2815407 - Confirmation of the protective effect of cysteamine in in vitro ultrasound exposures.
2766277 - Association among dna/chromosome break rejoining rates, chromatin structure alterations...
11166217 - Timing is everything: regulation of mitotic exit and cytokinesis by the men and sin.
3084637 - Effect of gamma radiation on resting b lymphocytes. i. oxygen-dependent damage to the p...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-10-20
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  131     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-05-28     Completed Date:  2012-07-30     Revised Date:  2014-09-29    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  582-90     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 UICC.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Adenocarcinoma / metabolism*,  pathology*
Androgens / metabolism
Cell Differentiation
Cell Line, Tumor
Heterogeneous-Nuclear Ribonucleoprotein K / metabolism
Mice, Inbred C57BL
Mice, Transgenic
Neuroendocrine Cells / metabolism*,  pathology
Prostatic Neoplasms / metabolism*,  pathology*
Proto-Oncogene Proteins c-akt / metabolism
Receptors, Androgen / metabolism
Signal Transduction*
beta Catenin / metabolism
Reg. No./Substance:
0/AR protein, human; 0/Androgens; 0/Heterogeneous-Nuclear Ribonucleoprotein K; 0/Receptors, Androgen; 0/beta Catenin; EC Proteins c-akt
Erratum In:
Int J Cancer. 2014 Nov 1;135(9):E9

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Formulation and evaluation of micro hydrogel of Moxifloxacin hydrochloride.
Next Document:  Genes related to diabetes may be associated with pancreatic cancer in a population-based case-contro...