Erkinheimo Tiina-Liisa, Lassus Heini, Sivula Anna, Sengupta Sibani, Furneaux Henry, Hla Timothy, Haglund Caj, Butzow Ralf, Ristimäki Ari
Department of Gynecology and Obstetrics, Helsinki University Central Hospital, University of Helsinki, FIN-00014 Helsinki, Finland.
Cancer Res. 2003 Nov 15;63(22):7591-4.
Cyclooxygenase-2 (COX-2) expression has been shown to associate with poor prognosis in ovarian cancer, and an mRNA stability protein HuR has been shown to enhance expression of COX-2 in tissue culture conditions. We found cytoplasmic immunoreactivity for HuR protein in 52% (233 of 445) of serous-type ovarian carcinoma specimens, and it associated with high COX-2 expression (P = 0.0045) and with clinicopathological variables, including poor prognosis (P < 0.0001) and high grade (P < 0.0001). In ovarian cancer cells in vitro, a small interfering RNA against HuR and leptomycin B, an inhibitor of nucleocytoplasmic translocation of HuR, inhibited COX-2 expression. Our results show that cytoplasmic HuR expression associates with poor outcome in ovarian cancer, and one plausible explanation for this finding may be related to the ability of HuR to induce COX-2 expression.
环氧化酶-2(COX-2)的表达已被证明与卵巢癌的不良预后相关,并且一种mRNA稳定性蛋白HuR已被证明在组织培养条件下可增强COX-2的表达。我们发现,在52%(445例中的233例)的浆液性卵巢癌标本中存在HuR蛋白的细胞质免疫反应性,并且它与高COX-2表达相关(P = 0.0045),还与临床病理变量相关,包括不良预后(P < 0.0001)和高级别(P < 0.0001)。在体外卵巢癌细胞中,针对HuR的小干扰RNA和HuR核质转运抑制剂 leptomycin B可抑制COX-2的表达。我们的结果表明,细胞质HuR表达与卵巢癌的不良结局相关,对此发现的一个合理的解释可能与HuR诱导COX-2表达的能力有关。