Eberhart C E, Coffey R J, Radhika A, Giardiello F M, Ferrenbach S, DuBois R N
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Gastroenterology. 1994 Oct;107(4):1183-8. doi: 10.1016/0016-5085(94)90246-1.
BACKGROUND/AIMS: Several clinical, epidemiological, and animal studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) may alter the incidence of colorectal cancer. A likely target for NSAIDs is cyclooxygenase, a key enzyme in arachidonic acid metabolism. Two isoforms of this enzyme have been identified; cyclooxygenase (COX) 1 and COX-2. The present study was undertaken to determine if there is differential expression of these isoforms in colorectal neoplasia, and, if so, at what stage in malignant transformation this occurs.
COX-1 and COX-2 messenger RNA (mRNA) levels were determined by Northern blot analysis of poly(A)+ RNA isolated from human colorectal cancers, adenomas, and accompanying normal mucosa.
There was a marked increase in COX-2 mRNA levels in 12 of 14 carcinomas (86%) compared with paired normal mucosa. In contrast, there was equivalent intensity of the COX-1 mRNA transcript between the normal mucosa and cancer in all 14 cases. In six pairs of colorectal adenomas and normal mucosa, three showed up-regulation of COX-2 in the adenoma compared with the normal mucosa. Because COX-2 expression is low to undetectable in normal colorectal mucosa, 14 unpaired adenomas were examined for COX-2 expression; a clearly detectable transcript was identified in six (43%).
COX-2, but not COX-1, gene expression is markedly elevated in most human colorectal cancers compared with accompanying normal mucosa. Furthermore, COX-2 expression seems to be increased in a subset of adenomas. COX-2 may provide an attractive therapeutic target in colorectal neoplasia.
背景/目的：多项临床、流行病学及动物研究表明，非甾体抗炎药（NSAIDs）可能会改变结直肠癌的发病率。NSAIDs的一个可能靶点是环氧化酶，它是花生四烯酸代谢中的关键酶。已鉴定出该酶的两种同工型；环氧化酶（COX）1和COX-2。本研究旨在确定这些同工型在结直肠肿瘤中是否存在差异表达，以及如果存在差异表达，这种情况发生在恶性转化的哪个阶段。
通过对从人结直肠癌、腺瘤及相应正常黏膜中分离的多聚腺苷酸（poly(A)+）RNA进行Northern印迹分析，来测定COX-1和COX-2信使核糖核酸（mRNA）水平。
与配对的正常黏膜相比，14例癌组织中有12例（86%）的COX-2 mRNA水平显著升高。相比之下，在所有14例病例中，正常黏膜和癌组织中COX-1 mRNA转录本的强度相当。在6对结直肠腺瘤和正常黏膜中，3对显示腺瘤中COX-2相对于正常黏膜上调。由于COX-2在正常结直肠黏膜中的表达很低或无法检测到，因此对14例未配对的腺瘤进行了COX-2表达检测；其中6例（43%）检测到明显可检测的转录本。
与相应的正常黏膜相比，大多数人结直肠癌中COX-2基因表达显著升高，而COX-1基因表达无明显变化。此外，一部分腺瘤中COX-2表达似乎也有所增加。COX-2可能为结直肠肿瘤提供一个有吸引力的治疗靶点。
