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J Cell Biol. 1999 Oct 4;147(1):71-6.

Sonic hedgehog opposes epithelial cell cycle arrest.

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1
VA Palo Alto Health Care System, Palo Alto, California 94304, USA.

Abstract

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.

PMID:
10508856
PMCID:
PMC2164980
[Indexed for MEDLINE]
Free PMC Article
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