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J. Biol. Chem., Vol. 281, Issue 33, 23676-23685, August 18, 2006

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Characterization of Human Mucin MUC17

COMPLETE CODING SEQUENCE AND ORGANIZATION^*

From the Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198

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, NFB, and Cdx-2 response elements.

Received for publication, January 11, 2006 , and in revised form, May 8, 2006.

^* This work was supported by National Institutes of Health (NIH) Grants CA111294, CA72712, CA78590, and P20RR16469, by Nebraska Department of Health and Human Services Grant 2005-16, and by NCI, NIH Cancer Center Grant P30 CA36727 to the University of Nebraska Medical Center. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the Gen-Bank^TM/EBI Data Bank with accession number(s) AJ606308 [GenBank] .

¹ Both authors contributed equally to this work.

² To whom correspondence should be addressed: Dept. of Biochemistry and Molecular Biology, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 985870 Nebraska Medical Center, Omaha, NE 68198-4525. Tel.: 402-559-5455; Fax: 402-559-6650; E-mail: sbatra{at}unmc.edu.

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