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  • Original Paper
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Normal and c-Myc-promoted human keratinocyte differentiation both occur via a novel cell cycle involving cellular growth and endoreplication

Abstract

The relationship between cell cycle and differentiation in human keratinocytes is poorly understood. It is believed that keratinocytes suppress DNA replication and cell cycle arrest in G0 before they initiate terminal differentiation. However, a temporal separation between both events has not been established. Moreover, c-Myc promotes keratinocyte differentiation without causing cell cycle arrest. To address these paradoxes we have analysed cell cycle control during normal and c-Myc-promoted differentiation. Continuous activation of c-Myc or initiation of terminal differentiation results in a block of G2/M, cellular growth, endoreplication and polyploidy. Keratinocytes abandon G1, continue replicating DNA as they differentiate terminally and become polyploid. In fact, simply blocking mitosis with nocodazole resulted in increased cell size, terminal differentiation and endoreplication. This indicates that terminal differentiation associates with defective cell cycle progression and provides a novel insight into c-Myc biology.

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Acknowledgements

The initial observations of this work were made in the laboratory of F Watt in ICRF of London, and A Gandarillas is especially grateful to her generosity and helpful suggestions. We thank C Brooks for some technical assistance, D Fisher for constructive suggestions and M Gomez and H Land for helpful comments at an early stage of the work. Thanks to JP Moles the data obtained from English skin could be displayed on French computers. A Gandarillas was funded by Bristol-Myers Squibb, ARC and EMBO. This research received financial support from CNRS and Ligue Nationale Contre le Cancer.

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Gandarillas, A., Davies, D. & Blanchard, JM. Normal and c-Myc-promoted human keratinocyte differentiation both occur via a novel cell cycle involving cellular growth and endoreplication. Oncogene 19, 3278–3289 (2000). https://doi.org/10.1038/sj.onc.1203630

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