Institute of Pathology, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin.
Histopathology. 2010 May;56(6):727-39. doi: 10.1111/j.1365-2559.2010.03544.x.
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.
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).
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.
功能研究表明，核因子（NF）-κB 可促进卵巢癌细胞的肿瘤进展。然而，人们对 NF-κB 通路效应物在人类卵巢癌中的表达知之甚少。
免疫组织化学和原位杂交显示，在 85 例原发性卵巢癌队列中，总 p65 表达与核和细胞质磷酸化 IkappaBalpha（分别为 P=0.002 和 P=0.05）和 IkappaBalpha mRNA 表达呈负相关（P=0.032）。相反，磷酸化 p65 的表达与核（P=0.027）和细胞质磷酸化 IkappaBalpha（P=0.01）的表达平行。总 p65 表达是总生存期的不良预后因素（P=0.018）。相反，总 IkappaBalpha 和磷酸化核和细胞质 IkappaBalpha 表达是有利的预后标志物（P=0.001，P=0.031，P=0.001，分别）。细胞质磷酸化 IkappaBalpha 表达在多变量分析中仍然是一个显著的预后因素（P=0.010）。在培养的、受刺激的 OVCAR-3 卵巢癌细胞中，核膜转运蛋白染色体区域维持/出口蛋白 1（CRM1）的抑制延迟了 p65 的细胞质再定位。在卵巢癌组织中证实了 p65 和 CRM1 表达之间的正相关（P<0.0001）。
总和磷酸化 IkappaBalpha 蛋白表达可能是人类卵巢癌中 NF-κB 激活的标志物。CRM1 过度表达的癌中 p65 的细胞质定位可能与核质转运失调有关。
