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Epidermal Ras blockade demonstrates spatially localized Ras promotion of proliferation and inhibition of differentiation

Oncogene volume 21, pages 1527–1538 (2002)Cite this article

Abstract

While important in carcinogenesis, the role of Ras in normal self-renewing tissues such as epidermis is unclear. To address this, we altered Ras function in undifferentiated and differentiating epidermal layers. Ras blockade within undifferentiated basal epidermal cells leads to decreased integrin expression, diminished growth capacity and induction of differentiation. Ras blockade in post-mitotic suprabasal epidermis exerts no effect. In contrast, regulated Ras and Raf activation inhibits differentiation. These findings indicate that spatially restricted Ras/Raf signaling divides epidermis into an undifferentiated proliferative compartment and a differentiating post-mitotic compartment and suggest a new role for Ras in tissue homeostasis.

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Acknowledgements

Supported by the USVA Office of Research and Development and AR43799 and AR45192, AR44012 from the NIAMS, NIH. M Dajee is a recipient of an NRSA Award from NIAMS. We thank M Lazarov, O Oro, J Ferrell, R Roth, Q Lin and D Kingsley for helpful discussions and pre-submission review. We thank E Fuchs for the K14 promoter, D Roop for the HK1 promoter, H Greulich for RasN17, M McMahon for Raf mutants, S Lowe for RasV12 and L Van Aelst for RasV12 S35, C40 and G37 mutants.

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Authors and Affiliations

  1. VA Palo Alto Healthcare System, Palo Alto, 94025, California, CA, USA

    Maya Dajee, Masahito Tarutani, Helen Deng, Ti Cai & Paul A Khavari

  2. Program in Epithelial Biology, Stanford University School of Medicine, Stanford, 94305, California, CA, USA

    Maya Dajee, Masahito Tarutani, Helen Deng, Ti Cai & Paul A Khavari

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  1. Maya Dajee
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  2. Masahito Tarutani
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Correspondence to Paul A Khavari.

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Dajee, M., Tarutani, M., Deng, H. et al. Epidermal Ras blockade demonstrates spatially localized Ras promotion of proliferation and inhibition of differentiation. Oncogene 21, 1527–1538 (2002). https://doi.org/10.1038/sj.onc.1205287

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