Basal cell carcinomas in mice overexpressing Gli2 in skin (original) (raw)

Nature Genetics volume 24, pages 216–217 (2000)Cite this article

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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Authors and Affiliations

  1. University of Michigan Comprehensive Cancer Center and Department of Dermatology, Ann Arbor, Michigan, USA
    Marina Grachtchouk & Andrzej A. Dlugosz
  2. Program in Developmental Biology, The Hospital for Sick Children, University of Toronto,
    Rong Mo, Sandy Yu, Xiaoyun Zhang & Chi-chung Hui
  3. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada
    Rong Mo, Sandy Yu, Xiaoyun Zhang & Chi-chung Hui
  4. Laboratory of Developmental Biology, Institute for Molecular and Cellular Biology, Osaka University, Osaka, Japan
    Hiroshi Sasaki

Authors

  1. Marina Grachtchouk
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  2. Rong Mo
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  3. Sandy Yu
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  4. Xiaoyun Zhang
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  5. Hiroshi Sasaki
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  6. Chi-chung Hui
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  7. Andrzej A. Dlugosz
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Correspondence toChi-chung Hui or Andrzej A. Dlugosz.

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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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