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

COX-1 或 COX-2 缺乏对小鼠皮肤癌的影响

• 批准号: 7593871
• 负责人: Robert Langenbach
• 金额: $ 18.3万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7593871
• 关键词: Back; Blood Vessels; Bromodeoxyuridine; Cells; Genotype; Goals; Incidence; Keratin; Modeling; Mus; Nude Mice; Numbers; PTGS2 gene; Process; Rate; Retroviridae; Role; Skin; Skin Cancer; cyclooxygenase 1; inhibitor/antagonist; keratinocyte; tumor; tumor growth; tumorigenesis

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.

用含有v-ras的逆转录病毒转染原代野生型COX-1-/-和COX-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，转染的COX-2 -/- 角质形成细胞的肿瘤生长明显减少，而COX-1-/- 角质形成细胞仅显示出轻微的肿瘤生长减少。移植了 COX-2 -/- 角质形成细胞的小鼠的肿瘤发生率也有所降低。每平方厘米肿瘤的血管数量不随角质形成细胞基因型而变化。与 WT 角质形成细胞相比，我们确实观察到 COX-2 -/- 角质形成细胞的增殖率较低，终末分化水平较高，如 BRDU 掺入量降低和角蛋白 1 表达增加所示。较低水平的细胞复制和增加的终末分化可能是COX-2-/-角质形成细胞在该移植模型中产生更少和更小的肿瘤的原因。