Upregulation of MUC6 mucin gene expression by NFκB and Sp factors

To clarify the mechanism underlying regulation of MUC6 expression, we isolated the 5′ flanking region of the MUC6 gene (5′-MUC6). We determined the transcription start site of the MUC6 gene, and found a TATA box at −35 to −29 bp, a putative NFκB consensus sequence at −173 to −164 bp, and putative Sp family binding sites at −530 to −521 and −847 to −838 bp. The luciferase activity of 5′-MUC6 gradually decreased with deletion of these sites. NFκB inhibitory factor IκB decreased the luciferase activity, and forced expression of NFκB induced MUC6 transcription. An inhibitor of Sp family binding, mithramycin A, suppressed MUC6 transcripts, and Sp1 and Sp3 overexpression up-regulated them. Binding of Sp family members to their putative sites was confirmed by electrophoretic mobility shift assays. Our results suggest that MUC6 transcription is regulated by NFκB and Sp family members.