Inverse expression of estrogen receptor-β and nuclear factor-κB in urinary bladder carcinogenesis

Inverse expression of estrogen receptor-β and nuclear factor-κB in urinary bladder carcinogenesis
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DOI:
10.1111/j.1442-2042.2010.02603.x
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发表时间:
2010-09-01
影响因子:
2.6
通讯作者:
Sotiropoulou-Bonikou, Georgia
Sotiropoulou-Bonikou, Georgia
中科院分区:
医学3区
文献类型:
--
作者:
Kontos, Stylianos;Kominea, Athina;Sotiropoulou-Bonikou, Georgia

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目的:根据临床病理特征,探讨核因子κB(NF-κB)和雌激素受体β(ER-β)信号通路在膀胱尿路上皮癌中的表达情况,阐明其在癌变过程中的作用。方法:对140例膀胱尿路上皮癌患者(男性94例,男性94例)的福尔马林固定石蜡切片进行免疫组化分析。 46 名女性)接受了经尿道膀胱肿瘤切除术。评估了 ER-β 和 NF-κ B 以及肿瘤分级和 T 期之间的相关性,以及人口统计数据、性别和年龄。结果:在细胞分化丧失期间(r(s) = -0.61,P 值 < 0.001,趋势检验 P 值 = 0.003)和肌肉浸润性癌(T2-T4;趋势检验 P 值 < ),膀胱细胞核中 ER-β 表达显着降低。 0.001)被发现。 NF-κB的p65亚基在膀胱上皮细胞的细胞核和细胞质中表达。肿瘤分级与 NF-κ B 核表达之间存在强正相关性。未观察到 NF-κ B、核或细胞质染色与 T 期之间的相关性。观察到 ER-β 与核 p65 免疫反应性之间呈负相关(r(s) = -0.45,P 值 < 0.001)。与人口统计数据没有相关性。结论:我们的免疫组织化学研究表明,NF-κ B 和 ER-β 转录因子在膀胱癌发生过程中可能存在反向调节。选择性 ER-β 激动剂和药物、NF-κ B 抑制剂可能代表膀胱尿路上皮肿瘤的一种可能的新治疗策略。
Objectives: To investigate the expression of nuclear factor-kappa B (NF-kappa B) and estrogen receptor-beta (ER-beta) signalling pathways in bladder urothelial carcinoma according to clinicopathological features, in order to elucidate their role during carcinogenesis.Methods: Immunohistochemical methodology was carried out on formalin-fixed, paraffin-embedded sections from urinary bladder carcinomas of 140 patients ( 94 males and 46 females) who underwent transurethral resection of bladder neoplasms. Correlations between ER-beta and NF-kappa B, and tumor grade and T-stage were evaluated, along with demographic data, sex and age.Results: A significant decrease in ER-beta expression in the nucleus of bladder cells during loss of cell differentiation (r(s) = -0.61, P-value < 0.001, test of trend P-value = 0.003) and in muscle invasive carcinomas (T2-T4; test of trend P-value < 0.001) was found. p65 Subunit of NF-kappa B was expressed in the nucleus and in the cytoplasm of bladder epithelial cells. A strong positive association between tumor grade and nuclear expression of NF-kappa B was shown. No correlation between NF-kappa B, nuclear or cytoplasmic staining, with T-stage was observed. An inverse correlation between ER-beta and nuclear p65 immunoreactivity was observed (r(s) = -0.45, P-value < 0.001). There was no correlation with demographic data.Conclusions: Our immunohistochemical study suggests the possible inverse regulation of NF-kappa B and ER-beta transcription factor during bladder carcinogenesis. Selective ER-beta agonists and agents, inhibitors of NF-kappa B, might represent a possible new treatment strategy for bladder urothelial tumors.