Characterization of human mucin MUC17. Complete coding sequence and organization.

With increasing interest on mucins as diagnostic and therapeutic targets in cancers and other diseases, it is becoming imperative to characterize novel mucins and investigate their biological significance. Here, we present the completed coding sequence and genomic organization of the previously published partial cDNA sequence of MUC17. Rapid amplification of cDNA ends with PCR, sequences from the Human Genome databases, and in vitro transcription/translational assays were used for these analyses. The MUC17 gene is located within a 39-kb DNA fragment between MUC12 and SERPINE1 on chromosome 7 in the region q22.1. The full-length coding sequence of MUC17 transcribes a 14.2-kb mRNA encompassing 13 exons. Alternate splicing generates two variants coding for a membrane-anchored and a secreted form. The canonical variable number of tandem repeats polymorphism of the central tandem repeat domain of the MUC genes is not significantly detected in the MUC17 gene. In addition, we show the overexpression of MUC17 by Western blot and immunohistochemical analyses in pancreatic tumor cell lines and tumor tissues compared with the normal pancreas. The expression of MUC17 is regulated by a 1,146-bp fragment upstream of MUC17 that contains VDR/RXR, GATA, NFkappaB, and Cdx-2 response elements.