Cyclin D1 overexpression in mouse epidermis increases cyclin-dependent kinase activity and cell proliferation in vivo but does not affect skin tumor development

In a previous study, we showed that synchronized proliferation of mouse epi dermis was induced by topical application of 12-O-tetradecanoyl-phorbol 13- acetate. Here, we used this system to study modifications in the cell cycle regulation and kinetics of proliferation in transgenic mice that overexpre ss cyclin D1 (K5D1 mice). Overexpression of cyclin D1 corresponded with an increase of proliferation in the epidermis of these transgenic mice. After proliferation reached its peak, the labeling index remained high in the tra nsgenics, but not in the wild-type animals. In addition, cyclin D1/cyclin-d ependent kinase (CDK) complex formation increased in the transgenic mice an d was correlated with elevated CDK4 and CDK6 kinase activities. However, th e increased CDK activities were not sufficient to effect mouse skin tumor d evelopment. In summary, these results show that cyclin D1 has a unique grow th-promoting role in tumor development, but does not act as an oncogene ind ependent of ras activity.