Document Detail

Expression of classical NF-kappaB pathway effectors in human ovarian carcinoma.
MedLine Citation:
PMID:  20546338     Owner:  NLM     Status:  MEDLINE    
AIMS: Functional studies have demonstrated that nuclear factor (NF)-kappaB promotes tumour progression in ovarian cancer cells. However, surprisingly little is known of the expression of effectors of the NF-kappaB pathway in human ovarian cancer in vivo. METHODS AND RESULTS: Immunohistochemistry and in situ hybridization revealed that in a cohort of 85 primary ovarian carcinomas, total p65 expression was inversely correlated to nuclear and cytoplasmic phospho-IkappaBalpha (P = 0.002 and P = 0.05, respectively), and IkappaBalpha mRNA expression (P = 0.032). In contrast, phospho-p65 expression was paralleled by the expression of nuclear (P = 0.027) and cytoplasmic phospho-IkappaBalpha (P = 0.01). Total p65 expression was an adverse prognostic factor for overall survival (P = 0.018). In contrast, total IkappaBalpha and phosphorylated nuclear and cytoplasmic IkappaBalpha expression were favourable prognostic markers (P = 0.001, P = 0.031, P = 0.001, respectively). Cytoplasmic phospho-IkappaBalpha expression remained a significant prognostic factor on multivariate analysis (P = 0.010). In cultured, stimulated OVCAR-3 ovarian cancer cells the cytoplasmic retranslocation of p65 was delayed by inhibition of the nuclear membrane transporter chromosomal region maintenance/exportin1 protein (CRM1). A positive association of p65 and CRM1 expression was demonstrated in ovarian cancer tissue (P < 0.0001). CONCLUSIONS: Total and phosphorylated IkappaBalpha protein expression might serve as markers for NF-kappaB activation in human ovarian carcinoma. Cytoplasmic localization of p65 may be related to deregulated nucleocytoplasmic transport in carcinomas overexpressing CRM1.
Silvia Darb-Esfahani; Bruno V Sinn; Wilko Weichert; Jan Budczies; Annika Lehmann; Aurelia Noske; Ann-Christin Buckendahl; Berit Maria Müller; Jalid Sehouli; Dominique Koensgen; Balazs Györffy; Manfred Dietel; Carsten Denkert
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Histopathology     Volume:  56     ISSN:  1365-2559     ISO Abbreviation:  Histopathology     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-06-15     Completed Date:  2010-11-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7704136     Medline TA:  Histopathology     Country:  England    
Other Details:
Languages:  eng     Pagination:  727-39     Citation Subset:  IM    
Institute of Pathology, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin.
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MeSH Terms
Carcinoma / genetics,  metabolism*,  pathology
Cell Line, Tumor
Cell Nucleus / metabolism
Cohort Studies
Cytoplasm / metabolism
Gene Expression Regulation, Neoplastic
I-kappa B Proteins / genetics,  metabolism
Karyopherins / genetics,  metabolism
NF-kappa B / metabolism*
Ovarian Neoplasms / genetics,  metabolism*,  pathology
RNA, Messenger / metabolism
Receptors, Cytoplasmic and Nuclear / genetics,  metabolism
Transcription Factor RelA / genetics,  metabolism
Reg. No./Substance:
0/I-kappa B Proteins; 0/Karyopherins; 0/NF-kappa B; 0/RNA, Messenger; 0/Receptors, Cytoplasmic and Nuclear; 0/Transcription Factor RelA; 0/exportin 1 protein; 139874-52-5/NF-kappaB inhibitor alpha

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