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The role of PI 3-kinase in the UVB-induced expression of c-fos

Oncogene volume 21, pages 2721–2728 (2002)Cite this article

Abstract

The role of the PI 3-kinase signaling pathway in UVB-induced c-fos gene expression was investigated in a human keratinocyte cell line, HaCaT. The enzymatic activity of PI 3-kinase was increased threefold by 250 J/m2 UVB. Inhibition of PI 3-kinase activity, via expression of a mutant p85 subunit or treatment with wortmannin, resulted in decreased levels of c-fos promoter activity and c-fos protein. Two members of the PI 3-kinase signaling pathway, Akt and GSK-3β, were also found to affect c-fos transactivation. Expression of dominant negative Akt or wild-type GSK-3β significantly inhibited UVB-induced c-fos promoter activity. In addition, when GSK-3β activity was inhibited by lithium chloride, both c-fos promoter activity and protein levels increased. These results demonstrate that both Akt activation and GSK-3β inactivation are required in the UVB-induction of c-fos. Our results demonstrate for the first time that UVB induction of c-fos is in part mediated by the PI 3-kinase signaling pathway in the HaCaT cell line. By identifying the multiple signaling pathways that are induced by UVB and contribute to the induction of c-fos expression, more drug targets may be identified to aid attempts to prevent and treat skin cancer.

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Abbreviations

UVB:

ultraviolet B

PI 3-kinase:

phosphatidylinositol 3′-kinase

CRE:

cyclic AMP-responsive element

CREB:

CRE binding protein

GSK-3β:

glycogen synthase kinase 3β

MAP:

mitogen-activated protein

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Acknowledgements

This work was supported in part by NCI Grant CA 27502 and a NRS Ford Minority Fellowship.

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  1. Department of Molecular and Cellular Biology, Arizona Cancer Center, College of Medicine, University of Arizona, Tucson, 85724, Arizona, AZ, USA

    Melissa Gonzales & G Tim Bowden

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  1. Melissa Gonzales
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  2. G Tim Bowden
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Correspondence to G Tim Bowden.

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Gonzales, M., Bowden, G. The role of PI 3-kinase in the UVB-induced expression of c-fos. Oncogene 21, 2721–2728 (2002). https://doi.org/10.1038/sj.onc.1205366

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