Enhanced Sp1 DNA-binding activity in murine keratinocyte cell lines and epidermal tumors

Altered regulation of ornithine decarboxylase (ODC) is frequently observed in epidermal tumors. We have shown that the transcription factor Spl is one of the regulators of ODC expression and that Sp3 antagonizes this Spl-medi ated activation of ODC expression. These results led us to examine the leve ls and binding activity of Spl and Sp3 in nuclear extracts prepared from cu ltured murine keratinocytes, transformed keratinocyte cell lines and epider mal tumors. Here we show that the Spl DNA-binding activity is higher in est ablished keratinocyte cell line extracts than in primary keratinocyte extra cts. Spl message levels and Spl DNA-binding activity was found to be low in 20-week papillomas and high in squamous cell carcinomas. These results sug gest that increased levels of Spl and enhanced Spl DNA binding activity are correlated with epidermal tumor progression. Based on these results, we pr opose that increased Spl DNA binding may augment the proliferative capacity of tumor cells through overexpression of Spl-responsive genes, possibly in cluding ODC. (C) 1999 Published by Elsevier Science Ltd. All rights reserve d.