Our long-term objectives are to understand the molecular mechanisms regulating the synthesis and secretion of gastrin, the gastrointestinal hormone. We will use in vitro molecular genetic gene transfer in cells and mouse embryos and in vitro transcription and protein-purification methods to elucidate the selective expression mechanisms of the human gastrin gene in differentiated cells. By expressing a selected oncogene in transgenic mice, we will generate antral mucosal and G-cell- specific tumors. This inherited mouse-tumor line will serve as a source of tissue to establish the G-cell line. The tumor tissue and G-cell line will be used for studies to define gastrin-gene expression mechanisms during development. The key components (DNA sequences and protein factors) of gastrin gene expression, both at the initiation and termination of transciption, will be identified and thoroughly characterized. The information thus gained and the availability of these purified components will facilitate in vitro reconstitution of the regulatory complex and will allow us to further determine the details of the biochemical mechanisms forming this precise and unique complex. This study will illuminate the fundamental features of cellular differentiation and will also provide important information for the understanding and eventual treatment of clinical disease. It may be possible, for example, to determine the cause of gastrinoma in pancreatic tissue.
