The long -range goal of this proposal is to continue to examine the functional and biochemical properties of the apical and basolateral plasmlemmal domains of the rat pancreatic acinar cell as they relate to stimulus-secretion coupling in a polarized glandular epithelial cell, and to define the factors involved in generation and maintenance of an organized epithelium both in the embryonic pancreas and in a rat acinar cell tumor. First, we plan to isolate and characterize biochemically the apical and basolateral plasmalemmal domains of the adult rat acinar cell preparatory to raising monoclonal antibodies for use in studies of apical/basolateral membrane biogenesis. Studies are also planned to characterize the topologic distribution and biochemical properties of the CCK receptor as an example of a specific basolateral membrane protein using autoradiography and affinity labeling with 125 I-labeled CCK-8 receptor probes. Second, we propose to characterize, using biochemical and immunochemical techniques, the properties of developmentally regulated plasmalemmal proteins that may be involved in cell-cell and cell-substratum interaction that accompany establishment of a polarized, functional epithelium in the embryonic rat pancreas including ontogeny of CCK receptors. Finally, using a transplantable rat acinar cell tumor whose cells reorganize into polarized epithelia in association with deposition of basal lamina when in contact with mesenchymally-derived tissues in vivo, we plan to examine directly in vitro the role of basal lamina and its components in establishment and maintenance of polarized epithelial structures and in regulatin of cell growth. These studies should further our understanding of the mechanisms wherein basal lamina mediates epithelial-mesenchymal interactions required for genesis of normal tissue architecture during pancreatic development and in the future may help in understanding potential aberrations of this interaction that may underly neoplastic transformation and developmental abnormalities.
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