Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Defective responses of transformed keratinocytes to terminal differentiation stimuli. Their role in epidermal tumour promotion by phorbol esters and by deep skin wounding

Abstract

Epidermal tumourigenesis can be achieved in rodents by the application of a single subthreshold dose of a carcinogen (initiation) followed by repeated applications of a tumour promoter such as 12-0-tetradecanoyl phorbol, 13-acetate (TPA). TPA induces terminal differentiation in the majority of epidermal keratinocytes in vitro. However, transformed keratinocytes respond weakly to this terminal differentiation signal, and it is suggested that this property allows initiated cells and their progeny to obtain a selective advantage over their normal counterparts during promotion of papilloma formation by TPA. New data are reviewed which suggest that a putative wound hormone TGF-beta has similar differential effects on normal and transformed epithelial cells to those of TPA. It is proposed that the release of TGF-beta from platelets following deep skin wounding may be an explanation as to why wounding is a promoting stimulus but milder forms of epidermal injury are not. Weakly promoting hyperplasiogenic agents are also discussed within the context of a selection theory of tumour promotion.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Parkinson, E. Defective responses of transformed keratinocytes to terminal differentiation stimuli. Their role in epidermal tumour promotion by phorbol esters and by deep skin wounding. Br J Cancer 52, 479–493 (1985). https://doi.org/10.1038/bjc.1985.219

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/bjc.1985.219

This article is cited by

Search

Quick links