Synchronized proliferation induced by 12-O-tetradecanoylphorbol-13-acetate treatment of mouse skin: an in vivo model for cell cycle regulation.
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.
Rodriguez-Puebla
M L
ML
The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville 78957, USA.
Robles
A I
AI
Johnson
D G
DG
LaCava
M
M
Conti
C J
CJ
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D016213:Cyclins / Q000378:metabolism; D005260:Female; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D016213:Cyclins; D016160:Retinoblastoma Protein; D013755:Tetradecanoylphorbol Acetate