The objectives of this research are to better define the antigens and genes of human pancreatic adenocarcinoma cells. Of particular interest are those genes and gene products related to transformation and differentiation of pancreatic ductal epithelial cells. To achieve the goals we propose to produce polyclonal and monoclonal antibodies to antigens of human pancreatic tumor lines which are related to differentiation. Some of these antigens are already defined by our existing murine DU-PAN monoclonal antibodies while others will be new. These studies also require molecular characterization and purification of the antigens. In addition, we propose to establish and characterize a unique series of tissue culture cell lines and clones which demonstrate differential expression of some genes and gene products related to differentiation and transformation of pancreatic ductal cells. These approaches include further characterization of existing clones of a pancreatic tumor cell line and production and characterization of new clones including clones with high metastatic potential. We will also attempt induction of differentiation with chemical agents and will produce and characterize human-hamster hybrid lines and clones. Finally, we propose to establish some cDNA and expression libraries which can be utilized for cloning genes coding for antigens defined by our antibodies and for identification of unique genes related to differentiation, metastases or transformation expressed in the clones and lines generated from this study.
