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Role of p38 MAP kinases and ERK in mediating ultraviolet-B induced cyclooxygenase-2 gene expression in human keratinocytes

Oncogene volume 20, pages 3921–3926 (2001)Cite this article

Abstract

The roles of p38 MAP kinases and ERK in UVB induced cox-2 gene expression were studied in a human keratinocyte cell line, HaCaT. UVB significantly increased cox-2 gene expression at both protein and mRNA levels. As we reported previously, p38 and ERK were significantly activated after UVB irradiation in HaCaT cells. In addition, treating the cells with p38 inhibitor SB202190 or MEK inhibitor PD98059 specifically inhibited UVB induced p38 or ERK activation, respectively. In this study, we further examined the roles of p38 and ERK in UVB induced cox-2 gene expression in HaCaT cells. We found that SB202190 strongly inhibited UVB induced COX-2 protein expression at different time points and various UVB doses. Furthermore, SB202190 markedly inhibited UVB induced cox-2 mRNA. Our data indicated that ERK did not play a role in UVB induced cox-2 gene expression in human keratinocytes since suppression of ERK did not significantly alter UVB induced increase of COX-2 protein and mRNA. These results suggested, for the first time, that activation of p38 is required for UVB induced cox-2 gene expression in human keratinocytes. Since cox-2 expression plays an important role in UV carcinogenesis, p38 could be a potential molecular target for chemoprevention of skin cancer.

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Acknowledgements

We thank Ms Anne Cione for secretarial assistance. This work was supported in part by NIH grant CA27502, Cancer Center Core Grant CA23074, and Center for Toxicology Grant p30 ESO6694.

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  1. Weixing Chen and Qingbo Tang: W Chen and Q Tang equally contributed to this study

Authors and Affiliations

  1. Department of Radiation Oncology, Arizona Cancer Center, College of Medicine, University of Arizona, Tucson, 85724, Arizona, AZ, USA

    Weixing Chen, Qingbo Tang, Melissa S Gonzales & G Tim Bowden

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  1. Weixing Chen
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  2. Qingbo Tang
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Chen, W., Tang, Q., Gonzales, M. et al. Role of p38 MAP kinases and ERK in mediating ultraviolet-B induced cyclooxygenase-2 gene expression in human keratinocytes. Oncogene 20, 3921–3926 (2001). https://doi.org/10.1038/sj.onc.1204530

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