Hwang D, Scollard D, Byrne J, Levine E
Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
J Natl Cancer Inst. 1998 Mar 18;90(6):455-60. doi: 10.1093/jnci/90.6.455.
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 anti-inflammatory 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 COX overexpression in this disease. This possibility led us to ask whether COX is also overexpressed in breast cancers.
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.
Expression of COX-1 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.
Our results suggest that overexpression of COX may not be unique to colon cancer and may be a feature common to other epithelial tumors.
大量研究表明，在包括乳腺癌和结肠癌在内的多种癌症中，前列腺素水平高于正常组织。特别是，作为前列腺素生物合成限速酶的诱导型环氧化酶（COX）在结肠肿瘤中过度表达。流行病学研究表明，使用阿司匹林或其他非甾体抗炎药（NSAIDs）可降低患结肠癌的风险，并在较小程度上降低患乳腺癌的风险。已知NSAIDs可抑制COX，这表明NSAIDs对结肠癌的有益作用可能与该疾病中COX的过度表达有关。这种可能性促使我们探究COX在乳腺癌中是否也过度表达。
对44例接受了肿块切除术或乳房切除术的乳腺癌患者的手术标本进行免疫印迹分析和免疫组织化学分析，以确定组成型表达的环氧化酶（COX-1）和诱导型（COX-2）的表达谱；14例患者的标本包括正常乳腺组织。
44个肿瘤样本中的30个样本中COX-1蛋白的表达明显高于14个正常组织标本中的任何一个。免疫印迹分析显示两个肿瘤样本中COX-2蛋白水平极高。对表达COX-1和/或COX-2的标本进行免疫组织化学染色显示，COX-1定位于肿瘤邻近的基质细胞而非肿瘤细胞中。相比之下，COX-2主要定位于肿瘤细胞中，但也出现在基质细胞中。
我们的结果表明，COX的过度表达可能并非结肠癌所特有，可能是其他上皮肿瘤的共同特征。
