Elevated cyclooxygenase-2 levels in Min mouse adenomas
Elevated cyclooxygenase-2 levels in Min mouse adenomas
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DOI：
10.1016/s0016-5085(96)70083-5
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发表时间：
1996-10-01
期刊：
影响因子：
29.4
通讯作者：
DuBois, RN
中科院分区：
文献类型：
--
作者：
Williams, CS;Luongo, C;DuBois, RN
背景与目的：APC 基因突变会导致肠肿瘤发生的可能性增加；然而，对导致肿瘤形成的机制的完整了解仍然难以捉摸，Min小鼠具有APC基因突变，并表现出与人类家族性腺瘤性息肉病中观察到的肿瘤表型相似的肿瘤表型，环氧合酶（COX）抑制剂降低了Min小鼠肠道中的肿瘤多样性。本研究旨在确定从Min小鼠肠道收获的腺瘤中COX-2是否增加。方法：通过Northern印迹和逆转录聚合酶链反应测定B6(Min) x 129小鼠源性肿瘤的COX-2信使RNA水平，通过Western印迹和免疫组织化学染色测定蛋白质水平和定位。结果：Northern 印迹显示，与正常粘膜相比，Min 小鼠腺瘤中的 COX-2 信使 RNA 水平增加了约三倍，与同一小鼠的正常粘膜相比，腺瘤组织中的 COX-2 蛋白水平也高出约三倍，使用单特异性 COX-2 抗体进行的免疫组织化学染色证实，COX-2 免疫反应性的增加仅限于肠粘膜内的发育不良和肿瘤病灶。 结论：这些数据表明 COX-2 水平可能增加在结直肠瘤形成的早期阶段，在息肉形成期间和侵袭之前。
Background & Aims: Mutations in the APC gene result in an increased propensity to develop intestinal neoplasia; however, a complete understanding of the mechanisms resulting in tumor formation has remained elusive, Min mice possess a mutation in the APC gene and display a neoplastic phenotype similar to that observed in familial adenomatous polyposis coli in humans, Cyclooxygenase (COX) inhibitors decrease tumor multiplicity in the Min mouse intestine, The present study was designed to determine if there was an increase in COX-2 in adenomas harvested from Min mouse intestine. Methods: COX-2 messenger RNA levels were determined by Northern blots and reverse-transcription polymerase chain reactions of B6(Min) x 129 mouse-derived tumors, Protein levels and localization were determined by Western blots and immunohistochemical staining. Results: The Northern blots revealed an approximately threefold increase in the level of COX-2 messenger RNA in Min mouse adenoma compared with normal mucosa, COX-2 protein levels in adenomatous tissues were also approximately threefold higher compared with normal mucosa from the same mouse, Immunohistochemical staining with a monospecific COX-2 antibody confirmed that increases in COX-2 immunoreactivity were restricted to dysplastic and neoplastic foci within intestinal mucosa, Conclusions: These data show that COX-2 levels may be increased at an early stage in colorectal neoplasia during polyp formation and before invasion.