| Expression of classical NF-kappaB pathway effectors in human ovarian carcinoma. | |
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MedLine Citation:
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PMID: 20546338 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article |
Journal Detail:
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Title: Histopathology Volume: 56 ISSN: 1365-2559 ISO Abbreviation: Histopathology Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-06-15 Completed Date: 2010-11-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7704136 Medline TA: Histopathology Country: England |
Other Details:
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Languages: eng Pagination: 727-39 Citation Subset: IM |
Affiliation:
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Institute of Pathology, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin. silvia.darb-esfahani@charite.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Carcinoma
/
genetics,
metabolism*,
pathology Cell Line, Tumor Cell Nucleus / metabolism Cohort Studies Cytoplasm / metabolism Female Gene Expression Regulation, Neoplastic Humans I-kappa B Proteins / genetics, metabolism Immunohistochemistry Karyopherins / genetics, metabolism NF-kappa B / metabolism* Ovarian Neoplasms / genetics, metabolism*, pathology Phosphorylation RNA, Messenger / metabolism Receptors, Cytoplasmic and Nuclear / genetics, metabolism Transcription Factor RelA / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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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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