DIFFERENTIAL EXPRESSION OF THE HUMAN GONADOTROPIN ALPHA-GENE IN ECTOPIC AND EUTOPIC CELLS

We have analyzed the regulation of the .alpha. gonadotropin gene in eutopic placental cells and ectopic tumor cells by constructing a series of plasmid vectors containing .alpha. genomic 5'' flanking DNA placed upstream of the gene encoding the bacterial enzyme chloramphenicol aetyltransferase (CAT). These plasmids DNAs were transfected into a eutopic (JAr) and an ectopic (HeLa) cell line. Both cell types expressed the CAT gene from plasmid constructs containing as much as 1,500 base pairs (bp) and as little as 140 bp of .alpha. 5'' flanking DNA; JAr cells were considerably more efficient than HeLa cells. Ectopic and eutopic cells differed qualitatively in their expression from these .alpha.-CAT constructs when cells were treated with cAMP or butyrate. Butyrate induced .alpha. expression in HeLa cells but not in JAr cells, while cAMP induced expression in JAr cells. These results are consistent with and extend previous observations suggesting that there are cell-specific differences in the regulation of .alpha. gene expression in ectopic and eutopic cells. However, by using deletion constructs of the .alpha.-CAT gene, we found that the basal expression and cell-specific induction of the .alpha. gene in ectopic and eutopic cells were dependent on the same 140 bp of .alpha. 5'' flanking DNA. These 140 bp were sequenced and found to contain a 9-bp stretch of DNA homologous with the consensus viral enhancer sequence. Such features of .alpha. expression common to both ectopic and eutopic cells may be involved in the coordinate expression of the .alpha. gene and the tumorigenic phenotype observed in each cell type.