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UVB induced cell cycle checkpoints in an early stage human melanoma line, WM35

Oncogene volume 19, pages 4480–4490 (2000)Cite this article

Abstract

The activation of cell cycle checkpoints in response to genotoxic stressors is essential for the maintenance of genomic integrity. Although most prior studies of cell cycle effects of UV irradiation have used UVC, this UV range does not penetrate the earth's atmosphere. Thus, we have investigated the mechanisms of ultraviolet B (UVB) irradiation-induced cell cycle arrest in a biologically relevant target cell type, the early stage human melanoma cell line, WM35. Irradiation of WM35 cells with UVB resulted in arrests throughout the cell cycle: at the G1/S transition, in S phase and in G2. G1 arrest was accompanied by increased association of p21 with cyclin E/cdk2 and cyclin A/cdk2, increased binding of p27 to cyclin E/cdk2 and inhibition of these kinases. A loss of Cdc25A expression was associated with an increased inhibitory phosphotyrosine content of cyclin E- and cyclin A-associated cdk2 and may also contribute to G1 arrest following UVB irradiation. The association of Cdc25A with 14-3-3 was increased by UVB. Reduced cyclin D1 protein and increased binding of p21 and p27 to cyclin D1/cdk4 complexes were also observed. The loss of cyclin D1 could not be attributed to inhibition of either MAPK or PI3K/PKB pathways, since both were activated by UVB. Cdc25B levels fell and the remaining protein showed an increased association with 14-3-3 in response to UVB. Losses in cyclin B1 expression and an increased binding of p21 to cyclin B1/cdk1 complexes also contributed to inhibition of this kinase activity, and G2/M arrest.

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Acknowledgements

JM Slingerland is a clinician investigator supported by Cancer Care Ontario, and by a career awards from the US Army Department of Defense Breast Cancer Research Program and from the Burroughs Wellcome Fund. We thank Dr N Bhattacharya for excellent technical assistance with tissue culture and irradiation of cells. This work was supported by grants to JM Slingerland from the CBCRI/National Cancer Institute of Canada.

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  1. Division of Cancer Biology Research, Toronto Sunnybrook Regional Cancer Centre, Sunnybrook and Women's College Health Sciences Centre and University of Toronto, Toronto, Ontario, Canada

    T Petrocelli & J Slingerland

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Petrocelli, T., Slingerland, J. UVB induced cell cycle checkpoints in an early stage human melanoma line, WM35. Oncogene 19, 4480–4490 (2000). https://doi.org/10.1038/sj.onc.1203808

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