Cytoplasmic induction and over-expression of cyclooxygenase-2 in human prostate cancer: implications for prevention and treatment
Cytoplasmic induction and over-expression of cyclooxygenase-2 in human prostate cancer: implications for prevention and treatment
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DOI：
10.1046/j.1464-410x.2000.00867.x
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发表时间：
2000-10-01
影响因子：
4.5
通讯作者：
Lalani, EN
中科院分区：
文献类型：
--
作者：
Madaan, S;Abel, PD;Lalani, EN
目的探讨环氧合酶(COX)-1和-2在人前列腺组织中的表达及形态分布，探讨其与前列腺癌Gleason分级的关系。材料与方法本研究选取30例良性前列腺增生（BPH）患者和82例前列腺癌患者。免疫组化检测COX-1和cox -2的表达，免疫印迹检测13个样本（6例BPH和7例癌症）。结果在前列腺增生和前列腺癌中，COX-1主要在纤维肌间质中表达，在腺/肿瘤上皮细胞中表达。相比之下，COX-2的表达在BPH和癌症之间存在显著差异。在BPH中，腔腺细胞中有COX-2的膜性表达，而间质无表达。在癌症中，COX-2的间质表达没有改变，但肿瘤细胞的表达明显增加（P = 0.008），染色模式从膜质变为细胞质（P < 0.001）。COX-2在低分化肿瘤中的表达明显高于高分化肿瘤（P < 0.001）。这些结果得到免疫印迹的支持，免疫印迹显示前列腺增生和癌症中COX-1的表达水平相似，但癌症中COX-2的表达是前列腺增生中COX-2的四倍。结论本研究首次评估了COX-1和COX-2蛋白在人良性和恶性前列腺中的共表达，发现COX-2在肿瘤中诱导并显著增高表达，且与肿瘤分级有关。经常使用非甾体类抗炎药与降低癌症发病率有关。目前的结果为COX-2抑制剂在预防和治疗前列腺癌中的潜在作用提供了基础。
Objective To assess the level and morphological distribution of cyclooxygenase (COX)-1 and -2 in human prostates and to determine any association with the Gleason grade of prostate cancer.Materials and methods The study comprised 30 samples from patients with benign prostatic hyperplasia (BPH) and 82 with prostate cancer. Immunohistochemistry was used to assess the expression of COX-1 and -2, and 13 samples were also assessed using immunoblotting (six BPH and seven cancers).Results For both BPH and prostate cancer, COX-1 expression was primarily in the fibromuscular stroma, with variable weak cytoplasmic expression in glandular/neoplastic epithelial cells. In contrast, COX-2 expression differed markedly between BPH and cancer. In BPH there was membranous expression of COX-2 in luminal glandular cells and no stromal expression. In cancer the stromal expression of COX-2 was unaltered, but expression by tumour cells was significantly greater (P = 0.008), with a change in the staining pattern from membranous to cytoplasmic (P < 0.001). COX-2 expression was significantly higher in poorly differentiated than in well differentiated tumours (P < 0.001). These results were supported by immunoblotting, which showed similar levels of COX-1 in both BPH and cancer, but four times greater expression of COX-2 in cancer than in BPH.Conclusion This is the first study to assess the co-expression of COX-1 and COX-2 proteins in benign and malignant human prostates, and showed the induction and significantly greater expression of COX-2 in cancer, which was also associated with tumour grade. The regular use of nonsteroidal anti-inflammatory drugs is associated with a reduced incidence of cancers. The present results provide the basis for a potential role for COX-2 inhibitors in the prevention and treatment of prostate cancer.