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PubMed · 10508856

Sonic hedgehog opposes epithelial cell cycle arrest.

H Fan·P A Khavari
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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.

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AnimalsCDC2-CDC28 KinasesCalciumBasal Cell CarcinomaCell CycleCell DifferentiationCell DivisionCells, CulturedCyclin-Dependent Kinase 2Cyclin-Dependent Kinase 4Cyclin-Dependent Kinase Inhibitor p21Cyclin-Dependent KinasesCyclinsEnzyme ActivationEpidermisHedgehog ProteinsHumansHyperplasiaKeratinocytesMiceMice, SCIDProtein Serine-Threonine KinasesProteinsProto-Oncogene ProteinsTrans-ActivatorsTransduction, GeneticJournal ArticleResearch Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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H Fan, P A Khavari. 1999-10-04. Sonic hedgehog opposes epithelial cell cycle arrest.. https://doi.org/10.1083/jcb.147.1.71

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