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© The Rockefeller University Press, 0021-9525/1999//71 $5.00
The Journal of Cell Biology, Volume 147, Number 1, , 1999 71-76

Sonic Hedgehog Opposes Epithelial Cell Cycle Arrest

^a VA Palo Alto Health Care System, Palo Alto, California 94304
^b Department of Dermatology, Stanford University School of Medicine, Stanford, California 94305
^c Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, California 94305
Stanford University School of Medicine, P204, MSLS Building, Stanford, CA 94305.(650) 723-8762(650) 725-5266

khavari{at}cmgm.stanford.edu

Stratified epithelium displays an equilibrium between proliferation and cell cycle arrest, a balance that is disrupted in basal cell carcinoma (BCC). Sonic hedgehog (Shh) pathway activation appears sufficient to induce BCC, however, the way it does so is unknown. Shh-induced epidermal hyperplasia is accompanied by continued cell proliferation in normally growth arrested suprabasal cells in vivo. Shh-expressing cells fail to exit S and G2/M phases in response to calcium-induced differentiation and also resist exhaustion of replicative growth capacity. In addition, Shh blocks p21^CIP1/WAF1-induced growth arrest. These data indicate that Shh promotes neoplasia by opposing normal stimuli for epithelial cell cycle arrest.

Key Words: Sonic hedgehog • epidermis • cell cycle regulation • basal cell carcinoma • cyclin-dependent kinase inhibitor

© 1999 The Rockefeller University Press

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