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Human melanocyte senescence and melanoma susceptibility genes

Oncogene volume 22, pages 3063–3069 (2003)Cite this article

Abstract

The molecular mechanisms and biology of cellular senescence in human melanocytes are discussed, including similarities to and differences from senescence in fibroblasts and other cell lineages. Special reference is made to the fact that the known melanoma susceptibility genes in the human, Inhibitor A of [cyclin-dependent] kinase 4–alternative reading frame (INK4A–ARF) and cyclin-dependent kinase 4, are involved in the regulation of cellular senescence, and possible reasons why this should be so. Based on the evidence including growth and survival kinetics of human and mouse melanocytes carrying germline deficiencies in the INK4A sequence, it is suggested that an ‘M0’ or p16/RB-dependent form of senescence may be particularly important in melanocytes. A speculative model is proposed, relating current concepts of early melanoma progression to the processes of cellular senescence and immortalization. This includes the suggestion that moles or nevi are senescent clones of melanocytes.

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Acknowledgements

We thank Estela Medrano, Rob Brooks and others for stimulating discussions. Work in the author's laboratory reviewed here was supported by Wellcome Trust Grant 046038/Z/95/Z and EC contract QLK4-1999-01084.

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  1. Department of Basic Medical Sciences, St George's Hospital Medical School, London, SW17 0RE, UK

    Dorothy C Bennett

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Correspondence to Dorothy C Bennett.

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Bennett, D. Human melanocyte senescence and melanoma susceptibility genes. Oncogene 22, 3063–3069 (2003). https://doi.org/10.1038/sj.onc.1206446

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