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-mediated activation of ODC expression. These results led us to examine the levels and binding activity of Spl and Sp3 in nuclear extracts prepared from cultured murine keratinocytes, transformed keratinocyte cell lines and epidermal tumors. Here we show that the Spl DNA-binding activity is higher in established keratinocyte cell line extracts than in primary keratinocyte extracts. 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 suggest that increased levels of Spl and enhanced Spl DNA binding activity are correlated with epidermal tumor progression. Based on these results, we propose that increased Spl DNA binding may augment the proliferative capacity of tumor cells through overexpression of Spl-responsive genes, possibly including ODC. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.