Polypeptide hormone regulation of gene transcription: specific 5' genomic sequences are required for epidermal growth factor and phorbol ester regulation of prolactin gene expression.

A fusion gene containing 5' rat prolactin genomic sequences ligated to the structural portion of the rat growth hormone gene ( grl ) was introduced by DNA-mediated gene transfer into mammalian cells by using a chimeric plasmid vector. Clonal transfected cell lines produced a mRNA that used the authentic 5' initiation site and that was processed to the predicted size. The intracellular levels of this RNA product were increased 2.5- to 5-fold by exposure of the cells to epidermal growth factor (EGF) and 2- to 3-fold by exposure of the cells to a potent phorbol ester, phorbol 12-myristate 13-acetate, apparently due to regulation at the level of gene transcription. Substitution of the 5' prolactin DNA sequences by 5' growth hormone DNA sequences resulted in the loss of EGF inducibility. A genomic sequence in or near the 5' flanking portion of the prolactin gene therefore appears to confer polypeptide hormone transcriptional regulation upon the gene.