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

将含有v-H-ras基因的逆转录病毒感染原代野生型和COX-2-/-角质形成细胞，并将其移植到裸鼠背部。与野生型角质形成细胞相比，转染型COX-2-/-角质形成细胞所产生的肿瘤发生率和肿瘤大小显著降低。与野生型角质形成细胞相比，COX-2-/-角质形成细胞的增殖率较低，终末分化水平较高。野生型和COX-2-/-肿瘤的血管形成程度和细胞凋亡水平相似，表明两者都不是缩小COX-2-/-肿瘤大小的因素。野生型和COX-2-/-肿瘤细胞中RAS的表达水平相似，而COX-2-/-角质形成细胞/肿瘤中p-EGFR和p-ERK1/2的表达水平低于野生型角质形成细胞/肿瘤，表明COX-2缺乏降低了促生长信号通路。因此，在转化的角质形成细胞中，COX-2的缺乏本身就足以减少肿瘤的生长，而不依赖于系统的COX-2表达。

Primary wild type and COX-2-/- keraticytes were transfected with a retrovirus containing v-H-ras and the transfected keratinocytes grafted on to the backs of athymic nude mice. Tumor incidence and tumor size resulting from transfected COX-2 -/- keratinocytes was markedly reduced compared to tumors produced by transfected wild type keratinocytes. Lower proliferation rates and higher levels of terminal differentiation were observed in the COX-2 -/- keratinocytes compared to wild type keratinocytes. The extent of vascularization and the levels of apoptosis were similar in wild type and COX-2-/- tumors, indicating that neither was not a factor in reducing COX-2-/- tumor size. While the levels of Ras were similar in wild type and COX-2-/- tumor cells, the levels of p-EGFR and p-ERK1/2 were lower in COX-2-/- keratinocytes/tumors compared to wild type keratinocytes/tumors indicating that COX-2 deficiency decreased growth promoting signaling pathways. Thus, the deficiency of COX-2 in the transformed keratinocyte itself was sufficient to decrease tumor growth independent of systemic COX-2 expression.