期刊
CELL CYCLE
卷 9, 期 16, 页码 3305-3314出版社
LANDES BIOSCIENCE
DOI: 10.4161/cc.9.16.12632
关键词
Cdk4(R24C); ras; melanoma; skin; carcinogen
类别
资金
- NIH [PO1 CA95569, RO1 AG22022]
The importance of the CDK4 protein in human cancer first became evident following the identification of a germ line mutation in the Cdk4 locus that predisposes humans to melanoma. This mutation results in substitution of arginine with cysteine at position 24 (R24C). In an earlier study, we introduced the R24C mutation into the Cdk4 locus of mice using Cre-loxP-mediated knock-in technology and observed a very low incidence of spontaneous melanomas in Cdk4(R24C/R24C) mice. This suggested that additional oncogenic mutations might be required for development of melanomas. Here we report an increased incidence of spontaneous cutaneous melanoma in mice expressing the oncogene HRAS(G12V) in melanocytes on a Cdk4(R24C) background. Treatment of Tyr-HRas: Cdk4(R24C/R24C) mice with the carcinogen, DMBA/TP A resulted in a further increase in the number of nevi and melanomas developed when compared with Tyr-HRas:Cdk4(+/+) mice. In summary, in Tyr-HRas: Cdk4(R24C/R24C) mice, we observed that activated CDK4 cooperates with the oncogenic HRAS(G12V) protein to increase the susceptibility of melanoma development in vivo.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据