Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer

Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer
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DOI:
10.1093/jnci/90.6.455
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发表时间:
1998-03-18
期刊:
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子:
--
通讯作者:
Levine, E
Levine, E
中科院分区:
其他
文献类型:
--
作者:
Hwang, D;Scollard, D;Levine, E

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背景资料:许多研究表明,在各种癌症中,包括乳腺癌和结肠癌,前列腺素的水平高于正常组织。特别是,诱导型环氧合酶(考克斯),前列腺素生物合成中的限速酶,在结肠肿瘤中过表达。流行病学研究表明,使用阿司匹林或其他非甾体类抗炎药(NSAID)可以降低结肠癌的风险,并在较小程度上降低乳腺癌的风险。已知NSAID可抑制考克斯,这表明NSAID在结肠癌中的有益作用可能与COS在该疾病中的过表达有关。方法:采用免疫印迹法和免疫组化法检测44例乳腺癌手术标本中组成型环氧合酶(考克斯-1)和诱导型环氧合酶(考克斯-2)的表达;结果:44例乳腺癌组织中有30例COX-1蛋白表达明显高于14例正常乳腺组织。免疫印迹分析显示两个肿瘤标本中考克斯-2蛋白表达水平极高。免疫组化染色显示考克斯-1和/或考克斯-2表达的标本显示考克斯-1定位于肿瘤旁的间质细胞而不是肿瘤细胞。相反,考克斯-2主要定位于肿瘤细胞,但也出现在间质细胞。结论:我们的结果表明,考克斯的过度表达可能不是唯一的结肠癌,可能是一个共同的特征,其他上皮性肿瘤。
Background: Numerous studies have demonstrated that the levels of prostaglandins are greater in various cancers, including breast cancer and colon cancer, than in normal tissues, In particular, the inducible form of cyclooxygenase (COX), the rate-limiting enzyme in prostaglandin biosynthesis, is overexpressed in colon tumors. Epidemiologic studies have demonstrated that the use of aspirin or other nonsteroidal antiinflammatory drugs (NSAIDs) can reduce the risk of colon cancer and, to a lesser extent, the risk of breast cancer. NSAIDs are known to inhibit COX, suggesting that the beneficial effect of NSAIDs in colon cancer may be related to COS overexpression in this disease. This possibility led us to ask whether COX is also overexpressed in breast cancers, Methods: Surgical specimens from 44 patients with breast cancer who had undergone lumpectomy or mastectomy were analyzed by immunoblot analysis and immunohistochemical analysis to determine the expression profile of the constitutively expressed form of cyclooxygenase (COX-1) and the inducible form (COX-2); the specimens from 14 patients included normal breast tissue, Results: Expression of COX-I protein was substantially higher in 30 of 44 tumor samples than in any of the 14 normal tissue specimens. Immunoblot analysis revealed extremely high levels of COX-2 protein in two tumor samples, Immunohistochemical staining of specimens that expressed COX-1 and/or COX-2 revealed that COX-1 was localized in stromal cells adjacent to the tumor but not in tumor cells. In contrast, COX-2 was localized primarily in tumor cells but also appeared in stromal cells, Conclusion: Our results suggest that overexpression of COX may not be unique to colon cancer and may be a feature common to other epithelial tumors.