Cellular Responses to Sodium Butyrate Exhibit the Dominance of One Parental Phenotype in Somatic Cell Hybrids

Abstract

The glycoprotein hormone α-subunit (GPHα) gene is inducible by sodium butyrate (NaBtr) in nontrophoblastic tumor cell lines such as HeLa (cervical carcinoma) but not in trophoblastic tumor cell lines such as JEG-3 (choriocarcinoma). The studies summarized in this report examined the ability of NaBtr to induce GPHα expression in somatic cell hybrids between HeLa SR3hyg and JEG-3neo. The hybrid cells, pooled clones resistant to both hygromycin B and G418 sulfate, have been named JELA and were indistinguishable from the SR3 parent with regard to induction of the GPHα gene. The effects of NaBtr on cell proliferation were also similar in HeLa and JELA but different from those in JEG-3. The GPHα gene could be induced by NaBtr in the JEG-3 parent only when they were simultaneously treated with cycloheximide (CHX). The ability of NaBtr to induce GPHα in CHX-treated JEG-3 cells occurred concomitantly with a change in the electrophoretic mobility of enhancer binding proteins as determined in gel shift assays. The DNA–protein complexes generated between a trophoblast specific element (TSE) and nuclear proteins in HeLa SR3 and JELA migrated significantly more slowly than the complex generated by JEG-3 nuclear proteins. However, when nuclear extracts were prepared from CHX-treated JEG-3 cells, the complex generated with the TSE oligonucleotide migrated more slowly than the complex from untreated JEG-3 cells and coincident with the complexes produced with nuclear extracts from HeLa SR3 and JELA cells. Together, these data demonstrate that inducibility of the GPHα gene by NaBtr in JELA cell hybrids resembles that of the HeLa SR3 parent and that its inducibility in the JEG-3 parent parallels the status of an enhancer binding protein (TSEB) as judged from changes in electrophoretic mobility. The results are consistent with a model in which the status of TSEB has a profound influence on the gene's response to NaBtr.