Cell Growth & Differentiation, Vol 9, Issue 1 31-39, Copyright © 1998 by American Association of Cancer Research

ARTICLES

Synchronized proliferation induced by 12-O-tetradecanoylphorbol-13-acetate treatment of mouse skin: an in vivo model for cell cycle regulation

ML Rodriguez-Puebla, AI Robles, DG Johnson, M LaCava and CJ Conti
The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville 78957, USA.

Much of what is known about the mammalian cell cycle comes from studies using established cell lines in culture. In this study, cell cycle-regulatory events were analyzed in vivo after treatment of mouse epidermis with 12-O-tetradecanoylphorbol-13-acetate. A synchronized wave of basal keratinocyte proliferation occurred; over 80% of the cells were in S phase 15 h after treatment. c-myc protein expression was induced, and p57Kip2 protein levels dropped early after stimulation. Before S phase, cyclin D1 and cyclin-dependent kinase (CDK) 6 levels increased, and expression of cyclins E and A was induced. Rb was phosphorylated in late G1, and this correlates with the formation of cyclin D1/CDK4 and cyclin D1/CDK6 complexes. At the end of S phase, the p57Kip2 and p21Cip1 protein levels increased. These findings demonstrate that stimulation of basal epidermal cells by 12-O-tetradecanoylphorbol-13-acetate results in several classic cell cycle events and suggests that p57Kip2 plays a key role in regulating proliferation in the epidermis.

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