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 Sp1 is one of the regulators of ODC expression and that Sp3 antagonizes this Sp1-mediated activation of ODC expression. These results led us to examine the levels and binding activity of Sp1 and Sp3 in nuclear extracts prepared from cultured murine keratinocytes, transformed keratinocyte cell lines and epidermal tumors. Here we show that the Sp1 DNA-binding activity is higher in established keratinocyte cell line extracts than in primary keratinocyte extracts. Sp1 message levels and Sp1 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 Sp1 and enhanced Sp1 DNA binding activity are correlated with epidermal tumor progression. Based on these results, we propose that increased Sp1 DNA binding may augment the proliferative capacity of tumor cells through overexpression of Sp1-responsive genes, possibly including ODC.
Kumar
A P
AP
Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Smithville 78957, USA. kumar@odin.mdacc.tmc.edu
Butler
A P
AP
D000818:Animals; D000831:Animals, Newborn; D001667:Binding, Competitive; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D002460:Cell Line; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D015603:Keratinocytes / Q000378:metabolism*; D051379:Mice; D018632:Mice, Inbred SENCAR; D009841:Oligonucleotides / Q000378:metabolism; D010212:Papilloma / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D012878:Skin Neoplasms / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism*
D009841:Oligonucleotides; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; D004247:DNA