The general purpose of this research is to understand the problem of differential gene activity in development and neoplasia, which results in the expression of diverse cellular phenotypes. Toward this aim, the regulation of the synthesis and secretion of serum proteins by liver cells will be further investigated. The effects of hormonally defined media, serum and other cellular factors on the expression of specific genes will be analyzed after mouse liver cell treatments in culture or after in vivo animal treatments. To characterize the molecular mechanisms of action, protein and RNA synthesis as well as their respective concentrations will be evaluated by immunoprecipitations, gel electrophoresis, molecular hybridizations or run on assays, using radioisotopes. Hepatoma cells will be used to test the hypothesis that cancer involves disorders in the gene expression regulatory patterns. In this relation, the reexpression of the AFP gene will be evaluated. Variants of the hepatoma OR-35775, negative and positive for AFP production, will be used to study the effects of hormones such as dexamethasone, cAMP, and estradiol. In addition, their interaction with the carcinogen L-ethionine will be determined. Other aspects of liver protein synthesis regulation will be investigated using the lizard Anolis pulchellus as an experimental model. The effects of serum components and hormones in protein synthesis and secretion rates will be looked at by culturing liver explants under different hormonal and serum treatments. The observed switching in the levels of albumin Vs Vitellogenin secretion under Estrogen will be studied to get information on the function of hormones in imposing short range changes in protein secretion patterns onto cells. The induction of female specific genes in newly hatch as well as male by estrogen will also be analyzed. Through this investigation, information directly pertinent to biomedical research related to cancer will be obtained. The experimental approach of using animal models to better understand basic cellular problems will be applied. This type of project is amenable for the training of students in the areas of cellular and molecular biology of biomedical sciences.
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