Abstract
Approximately 1,000,000 epithelial skin cancers are diagnosed in the United States each year and most are basal cell carcinomas (BCCs). The pathogenesis of these tumours involves constitutive activation of the Sonic hedgehog (Shh) signalling pathway (for review, see ref. 1). In many BCCs this can be attributed to loss-of-function mutations of PTCH (refs 2,3), which encodes a SHH receptor and antagonist. The specific downstream effector in the Shh pathway leading to cancer development is unknown. Here we show that transgenic mice overexpressing the transcription factor Gli2 in cutaneous keratinocytes develop multiple BCCs. These results establish Gli2 as a potent oncogene in skin and suggest a pivotal role for this transcription factor in the development of human BCC.
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Acknowledgements
We thank S. Yuspa, P. Coulombe, D. Bol and J. Jorcano for reagents; L. Lowe, L. Su and T. Johnson for advice on tumour histology; L. Wei and M. Berard for preparing the transgenic mice; and E. Fearon, G. Cotsarelis, S. Egan, S. Morrison and J.T. Elder for constructive comments on the manuscript. C.-c.H. was partially supported by the National Cancer Institute of Canada. A.A.D was supported in part by the University of Michigan Comprehensive Cancer Center (NIH CA46592) and Center for Organogenesis.
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Grachtchouk, M., Mo, R., Yu, S. et al. Basal cell carcinomas in mice overexpressing Gli2 in skin. Nat Genet 24, 216–217 (2000). https://doi.org/10.1038/73417
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DOI: https://doi.org/10.1038/73417
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