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Akt activation induces epidermal hyperplasia and proliferation of epidermal progenitors

Oncogene volume 26, pages 4882–4888 (2007)Cite this article

Abstract

Various common signaling pathways maintain tissue stem cells, including Notch and Wnt/β-catenin signals. Phosphoinositide-3 kinase (PI3K)/Akt signaling regulates the ‘stemness’ of several stem cells in culture, specifically in maintaining embryonic stem and neural stem cells, and in deriving embryonic germ cells from primordial germ cells. We examined the effect of Akt signaling in epidermal cells in transgenic mice expressing an Akt-Mer fusion protein whose kinase activity was conditionally activated by treatment with 4-hydroxytamoxifen (4OHT). The topical application of 4OHT to adult skin of the transgenic mice induced new hair growth in resting phase follicles. In addition, the mice showed hyperplasia in interfollicular epidermis (IFE) and hair follicles, which was presumably caused by the extensive proliferation of keratinocytes in basal layer of IFE and outer root sheath of hair follicles, respectively. The progenitor cell population increased consistently in 4OHT-treated transgenic mice. Our results show that PI3K/Akt signaling induces epidermal hyperplasia and proliferation of epidermal progenitors.

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Acknowledgements

We thank Ms A Kawai and Y Koreeda for assistance in generation of transgenic mice. KM is supported by scholarship from the Japanese Society for Promotion of Science. Animal care was in accordance with the guidelines of Osaka University. This work is supported in part by grants from the Ministry of Education, Science, Sports and Culture, Astellas Foundation for Research on Metabolic Disorders and the 21st Century COE ‘CICET’.

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Authors and Affiliations

  1. Department of Pathology, Graduate School of Medicine, Suita, Osaka, Japan,

    K Murayama, T Kimura & T Nakano

  2. Department of Dermatology, Graduate School of Medicine, Suita, Osaka, Japan,

    M Tarutani & I Katayama

  3. Department of Pathology Division, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan,

    M Tomooka & T Nakano

  4. Department of Ophthalmology and Visual Science, Graduate School of Medicine, Tohoku University, Aoba-ku, Sendai, Japan,

    R Hayashi & K Nishida

  5. Department of Experimental Genome Research, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan,

    M Okabe

  6. Department of Regenerative Dermatology, Graduate School of Medicine, Suita, Osaka, Japan,

    S Itami

Authors
  1. K Murayama
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  2. T Kimura
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  3. M Tarutani
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  4. M Tomooka
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  7. K Nishida
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  10. T Nakano
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Corresponding authors

Correspondence to T Kimura or T Nakano.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Murayama, K., Kimura, T., Tarutani, M. et al. Akt activation induces epidermal hyperplasia and proliferation of epidermal progenitors. Oncogene 26, 4882–4888 (2007). https://doi.org/10.1038/sj.onc.1210274

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