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

用含有v-H-ras的逆转录病毒转染原代野生型和考克斯-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。与由转染的野生型角质形成细胞产生的肿瘤相比，由转染的考克斯-2 -/-角质形成细胞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，在考克斯-2 -/-角质形成细胞中观察到较低的增殖率和较高水平的终末分化。野生型和考克斯-2-/-肿瘤中血管化程度和细胞凋亡水平相似，表明两者都不是减小考克斯-2-/-肿瘤大小的因素。虽然Ras水平在野生型和考克斯-2-/-肿瘤细胞中相似，但p-EGFR和p-ERK 1/2水平在考克斯-2-/-角质形成细胞/肿瘤中低于野生型角质形成细胞/肿瘤，表明考克斯-2缺乏降低了生长促进信号传导途径。 因此，转化的角质形成细胞本身中考克斯-2的缺乏足以降低肿瘤生长，而不依赖于全身性考克斯-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.