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Contribution of the MUC1 Tandem Repeat and Cytoplasmic Tail to Invasive and Metastatic Properties of a Pancreatic Cancer Cell Line¹

Eppley Institute for Research in Cancer and Allied Diseases, and the Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805 [K. G. K., A. J. G., M. H., M. D. B., S. K., D. L. K., T. C. C., M. A. H.], and Department of Preventive and Societal Medicine, Biostatistics Section, University of Nebraska Medical Center, Omaha, Nebraska 68191-4350 [J. L. M.]

MUC1 is a polymorphic, highly glycosylated, type I transmembrane protein expressed by ductal epithelial cells of many organs including pancreas, breast, gastrointestinal tract, and airway. MUC1 is overexpressed and differentially glycosylated by adenocarcinomas that arise in these organs, and is believed to contribute to invasive and metastatic potential by contributing to cell surface adhesion properties [via the tandem repeat (TR) domain] and through morphogenetic signal transduction [via the cytoplasmic tail (CT)]. The large extracellular TR of MUC1 consists of a heavily glycosylated, 20 amino acid sequence that shows allelic variation with respect to number of repeats. This portion of MUC1 may directly mediate adhesive or antiadhesive interactions with other surface molecules on adjacent cells and through these interactions initiate signal transduction pathways that are transmitted through the CT. We investigated the contribution of the TR domain and the CT of MUC1 to the in vivo invasive and metastatic potential, and the gene expression profile of the human pancreatic tumor cell line S2-013. Results showed that S2-013 cells overexpressing full-length MUC1 displayed a less invasive and metastatic phenotype compared with control-transfected cells and cells expressing MUC1 lacking the TR domain or CT. Clonal populations were analyzed by cDNA array gene expression analysis, which showed differences in the gene expression profiles between the different cell lines. Among the genes differentially expressed were several that encode proteins believed to play a role in invasion and metastasis.

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