Our studies have concerned regulation of gene expression during normal and abnormal differentiation processes. Hybridization and nuclease S1 mapping analysis demonstrated that 20S mature a-fetoprotein (AFP) and the 16S variant AFP mRNAS differ in sequences at the 5' end. The first six exons of the 20S mRNA were missing in the 16S RNA. We demonstrated that glucocorticoid hormone promotes matuation of fetal hepatocytes in vitro. Administration of glucocorticoid to differentiated fetal hepatocytes inhibited the production of fetal protein, AFP but induced the synthesis of tyrosine aminotransferase (TAT), an enzyme which appears only postnatally. Therefore, fetal cells matured into adult hepatocytes in the presence of glucocorticoid. The ts adult hepatocyte line expressed a large number of liver-specific functions. In addition to synthesizing AFP, albumin, and transferrin, these cells expressed genes encoding TAT, phosphoenolpyruvate carboxykinase (PEPCK), and fibrinogen. Furthermore, we showed that the expression of these genes was ts and glucocorticoid dependent. Genes encoding placental alkaline phosphatase (PAP) subunits were cloned. We found both choriocarcinoma and HeLa cells expressed different-sized PAP mRNA. Prednisolone and sodium butyrate which increased PAP biosynthesis in HeLa cells induced the expression of mature PAP mRNA. We cloned genes encoding pregnancy-specific Beta-1-glycoprotein (PSBetaG). These probes are used to examine molecular mechanism regulating PSBetaG synthesis in placental cells and fibroblasts.
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