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Macias E , Kim Y , de Marval PLM , Klein-Szanto A , Rodriguez-Puebla ML
Cdk2 deficiency decreases ras/CDK4-dependent malignant progression, but not myc-induced tumorigenesis
Cancer Research. 2007 Oct;67(20) :9713-9720
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We have previously shown that forced expression of CDK4 in mouse skin (K5CDK4 mice) results in increased susceptibility to squamous cell carcinoma (SCC) development in a chemical carcinogenesis protocol. This protocol induces skin papilloma development, causing a selection of cells bearing activating Ha-ras mutations. We have also shown that myc-induced epidermal proliferation and oral tumorigenesis (K5Myc mice) depends on CDK4 expression. Biochemical analysis of K5CDK4 and K5Myc epidermis as well as skin tumors showed that keratinocyte proliferation is mediated by CDK4 sequestration of p27(Kipl) and P21(Cipl), and activation of CDK2. Here, we studied the role of CDK2 in epithelial tumorigenesis. In normal skin, loss of CDK2 rescues CDK4-induced, but not mycinduced epidermal hyperproliferation. Ablation of CDK2 in K5CDK4 mice results in decreased incidences and multiplicity of skin tumors as well as malignant progression to SCC. Histopathologic analysis showed that K5CDK4!
Macias, Everardo Kim, Yongbaek de Marval, Paula L. Miliani Klein-Szanto, Andres Rodriguez-Puebla, Marcelo L. AMER ASSOC CANCER RESEARCH