Heterogeneous (positional) expression of hepatic glutamine synthetase: features, regulation and implications for...

Glutamine synthetase expression in liver parenchyma is restricted to a small population of pericentral hepatocytes surrounding the central veins. Studies on the development of this heterogeneous (positional) gene expression and of the changes observed in response to experimental alterations of liver physiology or manipulations of hepatocytes in culture have revealed that it is dependent on cell-cell and cell-matrix interactions rather than on the levels of hormones and other modulating factors. The considerable stability of GS expression may point to further events leading to a defined differentiated GS+ phenotype. Observations during experimental hepatocarcinogenesis indicate that strong GS expression may be used for tracing hepatocellular lineages during preneoplastic and early neoplastic stages. Furthermore, these studies suggest a relationship between the GS+ phenotype and enhanced growth of these lesions. Future studies should help to define the diagnostic value of GS and its significance for new chemotherapeutic strategies.