8-Cl-adenosine induces growth arrest without differentiation of primary mouse epidermal keratinocytes.
J Invest Dermatol
; 117(6): 1588-93, 2001 Dec.
Article
en En
| MEDLINE
| ID: mdl-11886527
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 IC(50) of 7.5 microM, 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 microM 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 non-transformed/non-immortalized cell system, possibly through an elevation in p21(WAF1/Cip1) protein levels, without inducing differentiation.
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Base de datos:
MEDLINE
Asunto principal:
8-Bromo Monofosfato de Adenosina Cíclica
/
Queratinocitos
/
Antineoplásicos
Límite:
Animals
Idioma:
En
Revista:
J Invest Dermatol
Año:
2001
Tipo del documento:
Article
País de afiliación:
Estados Unidos