Cyclooxygenases expression and distribution in the normal ovary and their role in ovarian cancer in the domestic hen (Gallus domesticus)
Cyclooxygenases expression and distribution in the normal ovary and their role in ovarian cancer in the domestic hen (Gallus domesticus)
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DOI：
10.1007/s12020-008-9080-z
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发表时间：
2008-06-01
期刊：
影响因子：
3.7
通讯作者：
Bahr, Janice M.
中科院分区：
文献类型：
--
作者：
Hales, Dale Buchanan;Zhuge, Yan;Bahr, Janice M.
环氧合酶（考克斯）（PTGS）是洋地黄素生物合成的限速酶。已经鉴定了两种考克斯异构体，考克斯-1和考克斯-2，其显示不同的细胞特异性表达和调节。卵巢癌是最致命的妇科恶性肿瘤，由于缺乏合适的动物模型，对该疾病的了解很少。产蛋者自发地发展上皮性卵巢癌，很少或没有症状，直到癌症进展到晚期，类似于人类疾病。本研究的目的是检测考克斯-1和考克斯-2在正常母鸡卵巢和卵巢癌组织中的相对表达和分布。结果表明，考克斯-1在正常卵巢的颗粒细胞层、皮质层、卵巢表面上皮（OSE）和排卵后卵泡（POF）均有表达。在卵巢癌中，考克斯-1 mRNA显著增加，考克斯-1蛋白广泛分布于整个肿瘤间质。考克斯-2蛋白定位于卵泡和卵巢间质的颗粒细胞层。考克斯-2 mRNA的表达没有改变作为一个功能的年龄或卵巢癌。首次POF（POF-1）中考克斯-1 mRNA的表达显著高于POF-2和POF-3。POFs中考克斯-2 mRNA的表达无明显差异。在从卵泡层次中的单个卵泡分离的OSE中，考克斯-1或考克斯-2 mRNA没有差异。这些结果证实了先前的发现，即考克斯-1在卵巢肿瘤中的高表达，进一步支持了产蛋鸡作为卵巢癌模型，并首次证明了考克斯-1在POF-1中的高表达，POF-1是产卵所需的前列腺素的来源。
Cyclooxygenase (COX) (PTGS) is the rate-limiting enzyme in the biosynthesis of prostaglandins. Two COX isoforms have been identified, COX-1 and COX-2, which show distinct cell-specific expression and regulation. Ovarian cancer is the most lethal gynecological malignancy and the disease is poorly understood due to the lack of suitable animal models. The laying lien spontaneously develops epithelial ovarian cancer with few or no symptoms until the cancer has progresses to a late stage, similar to the human disease. The purpose of this study was to examine the relative expression and distribution of COX-1 and COX-2 in the ovaries of normal hens and in liens with ovarian cancer. The results demonstrate that COX-1 was localized to the granulosa cell layer and cortical interstitium, ovarian surface epithelium (OSE) and postovulatory follicle (POF) of the normal ovary. In ovarian cancer, COX-1 mRNA was significantly increased and COX-1 protein was broadly distributed throughout the tumor stroma. COX-2 protein was localized to the granulosa cell layer in the follicle and the ovarian stroma. COX-2 mRNA expression did not change as a function of age or in ovarian cancer. There was significantly higher expression of COX-1 mRNA in the first POF (POF-1) compared to POF-2 and POF-3. COX-2 mRNA expression was not significantly different among POFs. There was no difference in COX-1 or COX-2 mRNA in the OSE isolated from individual follicles in the follicular hierarchy. The results confirm previous findings of the high expression of COX-1 in ovarian tumors further supporting the laying hen as a model for ovarian cancer, and demonstrate for the first time the high expression of COX-1 in POF-1 which is the source of prostaglandins needed for oviposition.