Abstract
The growth of ‘differentiated’ Faza 967 and ‘dedifferentiated’ H56 clones of H4IIEC3 rat hepatoma cell line is inhibited by dexamethasone via specific glucocorticoid receptors. We have isolated a series of growth-resistant variants from the growth—sensitive parental clones. The variants were either receptor—deficient or displayed significant, but reduced steroid binding capacity. The receptor containing variants of Faza 967 cells retained the inducibility of tyrosine aminotransferase for several months demonstrating the separation of different glucocorticoid receptor mediated functions. Alpha—fetoprotein (AFP) synthesis, which was not observed in the Faza 967 cells have been activated in the variants upon cultivation for several months in the presence of dexamethasone, but was extinguished — like the other liver specific functions — after long term cultivation. These variants offer a valuable model system for studying regulatory mechanisms involved in the activation and inactivation of genes coding for liver—specific proteins. Somatic cell hybrids between AFP and albumin producing and non—producing hepatoma clones produced none of these proteins. The extinction of AFP and albumin synthesis in hybrids is transcriptionally regulated similarly to that of the regulation in AFP and albumin non producing hepatoma cells. When assayed for methylation of the CCGG sequences of the variant clones and hybrids using the restriction enzyme isoschizomers HpaII and MspI we found that two methylation sites in the 5′ region of the AFP gene and one in exon 1 of the albumin gene were methylated in the non—expressing and demethylated in the expressing cells. Our results support the notion that alteration of methylation pattern at specific sites correlates well with AFP and albumin gene expression in different hepatoma cell lines and hybrid clones.
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Venetianer, A., David, D. (1990). Regulation of Liver Gene Expression in Dexamethasone Resistant Hepatoma Cells. In: Alexis, M.N., Sekeris, C.E. (eds) Activation of Hormone and Growth Factor Receptors. NATO ASI Series, vol 295. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-1936-5_15
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DOI: https://doi.org/10.1007/978-94-009-1936-5_15
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