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

摘要

The glycoprotein hormone a-subunit (GPHa) gene is inducible by sodium butyrate (NaBtr) in nontropho- blastic tumor cell lines such as HeLa (cervical carci- noma) 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 GPHa expression in somatic cell hybrids between HeLa SR3hyg and JEG-3neo. The hybrid cells, pooled clones resistant to both hygromycin Band G418 sul- fate, have been named JELA and were indistinguish- able from the SR3 parent with regard to induction of the GPHa gene. The effects of NaBtr on cell prolifera- tion were also similar in HeLa and JELA but different from those in JEG-3. The GPHa 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 GPHa in CHX-treated JEG-3 cells occurred concomitantly with a change in the electrophoretic mobility of enhancer binding pro- teins 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 pro- teins. 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 co- incident with the complexes produced with nuclear extracts from HeLa SR3 and JELA cells. Together, these data demonstrate that inducibility of the GPHa 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 bind- ing protein (TSEB) as judged from changes in electro- phoretic 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.