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- Title
Expression of classical NF-κB pathway effectors in human ovarian carcinoma.
- Authors
Darb-Esfahani, Silvia; Sinn, Bruno V.; Weichert, Wilko; Budczies, Jan; Lehmann, Annika; Noske, Aurelia; Buckendahl, Ann-Christin; Müller, Berit Maria; Sehouli, Jalid; Koensgen, Dominique; Györffy, Balazs; Dietel, Manfred; Denkert, Carsten
- Abstract
Darb-Esfahani S, Sinn B V, Weichert W, Budczies J, Lehmann A, Noske A, Buckendahl A-C, Müller B M, Sehouli J, Koensgen D, Györffy B, Dietel M & Denkert C (2010) Histopathology 56. 727–739 Expression of classical NF-κB pathway effectors in human ovarian carcinoma Aims: Functional studies have demonstrated that nuclear factor (NF)-κB promotes tumour progression in ovarian cancer cells. However, surprisingly little is known of the expression of effectors of the NF-κB 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-IκBα ( P = 0.002 and P = 0.05, respectively), and IκBα mRNA expression ( P = 0.032). In contrast, phospho-p65 expression was paralleled by the expression of nuclear ( P = 0.027) and cytoplasmic phospho-IκBα ( P = 0.01). Total p65 expression was an adverse prognostic factor for overall survival ( P = 0.018). In contrast, total IκBα and phosphorylated nuclear and cytoplasmic IκBα expression were favourable prognostic markers ( P = 0.001, P = 0.031, P = 0.001, respectively). Cytoplasmic phospho-IκBα 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 IκBα protein expression might serve as markers for NF-κB activation in human ovarian carcinoma. Cytoplasmic localization of p65 may be related to deregulated nucleocytoplasmic transport in carcinomas overexpressing CRM1.
- Subjects
OVARIAN cancer; GENE expression; CANCER genetics; CANCER invasiveness; CANCER cell growth; IMMUNOHISTOCHEMISTRY; DIAGNOSTIC use of in-situ hybridization
- Publication
Histopathology, 2010, Vol 56, Issue 6, p727
- ISSN
0309-0167
- Publication type
Article
- DOI
10.1111/j.1365-2559.2010.03544.x