In addition to their importance and biological role in the lubrication and protection of normal epithelial tissues, mucins comprise an important class of tumor associated antigens. As part of the continuing investigation of the DuPan-2 antigen, we have cloned and sequenced the full length cDNA for the pancreatic tumor mucin (MUC1) on which this antigen was expressed. Recently, we have inserted the full length mucin cDNA into both prokaryotic and eukaryotic expression vectors and achieved stable high level expression of recombinant mucin in both systems. The stable expression of MUC1 protein in a previously nonexpressing undifferentiated pancreatic tumor cell line resulted in morphological changes in the cells which may be characteristic of a differentiated, secretory state. The studies proposed within will employ expression studies with mutated MUC1 constructs to evaluate the relationships between structure of the MUC1 protein, it's post-translational processing and secretion by different normal and tumor epithelial cells, and the relationship of these to the observed alterations of differentiated morphology and growth properties in transfected cells. In addition, monoclonal antibody reagents will be developed using recombinant protein which will be of use in investigating the post-translational processing of the MUC1 protein and which may also be of diagnostic and therapeutic usefulness for the treatment of pancreatic adenocarcinoma.
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