8-Cl-adenosine induces growth arrest without differentiation of primary mouse epidermal keratinocytes

Daniel T. Dransfield, Richard D. Griner, Sagarika Ray, Meral Keskintepe, Wendy B. Bollag

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

In some cell systems, the antiproliferative effects of 8-Cl-cAMP, a site-selective cAMP analog specific for the type I cAMP-dependent protein kinase, are mediated by its metabolite, 8-Cl-adenosine. These effects were once thought to be specific to transformed cells. We investigated the ability of 8-Cl-adenosine to regulate growth and differentiation in primary cultures of mouse epidermal keratinocytes. A 24 h exposure of keratinocytes to 8-Cl-adenosine inhibited [3H]thymidine incorporation in a dose-dependent manner with an apparent IC50 of 7.5 μM, and these effects were completely reversible. To determine the ability of 8-Cl-adenosine to induce differentiation of primary keratinocytes, we measured keratin-1 expression and transglutaminase activity, markers of early and later stages of keratinocyte differentiation, respectively. Interestingly, exposure of keratinocytes to 25 μM 8-Cl-adenosine for 24 h had no effect on keratin-1 expression or transglutaminase activity. The 8-Cl-adenosine-induced growth arrest of keratinocytes required uptake of the compound and was accompanied by an increase in protein expression of the cyclin-dependent protein kinase inhibitor p21 WAF1/Cip1. These results demonstrate that 8-Cl-adenosine inhibits growth in a nontransformed/non-immortalized cell system, possibly through an elevation in p21WAF1/Cip1 protein levels, without inducing differentiation.

Original languageEnglish (US)
Pages (from-to)1588-1593
Number of pages6
JournalJournal of Investigative Dermatology
Volume117
Issue number6
DOIs
Publication statusPublished - Dec 2001

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Keywords

  • Cell cycle
  • Keratin-1
  • P21
  • Transglutaminase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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