Document Detail


The role of c-Jun and c-Fos expression in androgen-independent prostate cancer.
MedLine Citation:
PMID:  15378488     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Molecular mechanisms underlying the development of androgen-insensitive prostate cancer (AIPC) are poorly understood. However, there is growing evidence that different molecular profiles may result in the development of AIPC. Cell line studies demonstrate that c-Jun and c-Fos, via formation of the transcription factor activated protein 1 (AP-1), activate androgen-regulated genes independent of androgens and that c-Jun alone acts as an androgen receptor co-factor. The aim of this study was to investigate whether increased levels of c-Jun and phosphorylated c-Jun are associated with the development of AIPC using clinical material. Material from a cohort of 51 patients with paired tumours, obtained before and after the development of AIPC, and with full clinical biochemical follow-up, was retrieved from the archives. Tumour c-Jun, activated c-Jun, c-Fos, and pan protein kinase C (PKC) protein expression were analysed by immunohistochemistry and protein expression was scored by two independent observers using a weighted histoscore. No evidence was found to suggest that c-Jun acting as an androgen receptor co-factor influences the development of AIPC. However, it was observed that patients with high expression levels of phosphorylated c-Jun had a significantly shorter survival from relapse compared with patients with low phosphorylated c-Jun protein expression (p = 0.023), suggesting that increased AP-1 levels may promote AIPC tumour growth. Whilst PKC did not appear to activate c-Jun in vivo, increased PKC expression in AIPC tumours was also associated with decreased patient survival from time of relapse (p = 0.014). In conclusion, the data support the hypothesis that activation of c-Jun plays a role in the development of AIPC via AP-1 formation in some patients. However, PKC appears to promote the development of AIPC independently of c-Jun activation via an as yet unexplained mechanism.
Authors:
Joanne Edwards; N Sarath Krishna; Rono Mukherjee; John M S Bartlett
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of pathology     Volume:  204     ISSN:  0022-3417     ISO Abbreviation:  J. Pathol.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-09-24     Completed Date:  2005-03-25     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0204634     Medline TA:  J Pathol     Country:  England    
Other Details:
Languages:  eng     Pagination:  153-8     Citation Subset:  IM    
Affiliation:
Endocrine Cancer Group, Section of Surgical and Translational Research, University of Glasgow, Glasgow Royal Infirmary, Glasgow, G31 2ER, UK. jel0b@clinmed.gla.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Aged
Androgens / physiology*
Humans
Male
Neoplasm Proteins / analysis*
Neoplasm Recurrence, Local
Phosphorylation
Prostatic Neoplasms / chemistry*,  mortality,  physiopathology
Protein Kinase C / metabolism
Proto-Oncogene Proteins c-fos / analysis*
Proto-Oncogene Proteins c-jun / analysis*
Retrospective Studies
Survival Analysis
Transcription Factor AP-1 / analysis
Chemical
Reg. No./Substance:
0/Androgens; 0/Neoplasm Proteins; 0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-jun; 0/Transcription Factor AP-1; EC 2.7.11.13/Protein Kinase C

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