Effects of COX-1 or COX-2 Deficiency on Mouse Skin Cancer

用含有v-ras的逆转录病毒转染原代野生型、考克斯-1-/-和考克斯-2-/-角质形成细胞，并将转染的角质形成细胞移植到无胸腺裸鼠的背部。与转染的WT相比，来自转染的考克斯-2 -/-角质形成细胞的肿瘤生长显著降低，而考克斯-1-/-角质形成细胞仅显示出轻微降低的肿瘤生长。在移植有考克斯-2-/-角质形成细胞的小鼠中肿瘤发生率也降低。每平方厘米肿瘤的血管数与角质形成细胞基因型没有差异。与WT角质形成细胞相比，我们确实观察到考克斯-2 -/-角质形成细胞中较低的增殖率和较高的终末分化水平，如通过BRDU掺入降低和角蛋白1表达增加所指示的。较低水平的细胞复制和增加的终末分化可能是考克斯-2-/-角质形成细胞在该移植模型中产生较少和较小肿瘤的原因。

Primary wild type, COX-1-/- and COX-2-/- keraticytes were transfected with a retrovirus containing v-ras and the transfected keratinocytes grafted on to the back of athymic nude mice. Tumor growth from transfected COX-2 -/- keratinocytes was markedly reduced compared to transfected WT, while COX-1-/- keratinocytes showed only slightly reduced tumor growth. Tumor incidence was also reduced in mice grafted with the COX-2 -/- keratinocytes. The number of blood vessels per square cm of tumor did not differ with keratinocyte genotype. We did observe lower proliferation rates and higher levels of terminal differentiation in the COX-2 -/- keratinocytes compared to WT keratinocytes as indicated by lowed BRDU incorporation and increased keratin 1 expression. The lower levels of cell replication and increased terminal differentiation were likely causes of COX-2-/- keratinocytes giving rise to fewer and smaller tumors in this grafting model.