CDK4 coexpression with Ras generates malignant human epidermal tumorigenesis
Author: ["Mirella Lazarov","Yoshiaki Kubo","Ti Cai","Maya Dajee","Masahito Tarutani","Qun Lin","Min Fang","Shiying Tao","Cheryl L. Green","Paul A. Khavari"]
Publication: Nature Medicine
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Abstract
Ras acts with other proteins to induce neoplasia. By itself, however, strong Ras signaling can suppress proliferation of normal cells. In primary epidermal cells, we found that oncogenic Ras transiently decreases cyclin-dependent kinase (CDK) 4 expression in association with cell cycle arrest in G1 phase. CDK4 co-expression circumvents Ras growth suppression and induces invasive human neoplasia resembling squamous cell carcinoma. Tumorigenesis is dependent on CDK4 kinase function, with cyclin D1 required but not sufficient for this process. In facilitating escape from G1 growth restraints, Ras and CDK4 alter the composition of cyclin D and cyclin E complexes and promote resistance to growth inhibition by INK4 cyclin-dependent kinase inhibitors. These data identify a new role for oncogenic Ras in CDK4 regulation and highlight the functional importance of CDK4 suppression in preventing uncontrolled growth.
Cite this article
Lazarov, M., Kubo, Y., Cai, T. et al. CDK4 coexpression with Ras generates malignant human epidermal tumorigenesis. Nat Med 8, 1105–1114 (2002). https://doi.org/10.1038/nm779
