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.
D001483:Base Sequence; D002294:Carcinoma, Squamous Cell; D002460:Cell Line; D002999:Clone Cells; D003001:Cloning, Molecular; D004262:DNA Restriction Enzymes; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005796:Genes / Q000187:drug effects*; D005822:Genetic Vectors; D013006:Growth Hormone / Q000235:genetics*; D006801:Humans; D010704:Phorbols / Q000494:pharmacology*; D011388:Prolactin / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection
D010704:Phorbols; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D011388:Prolactin; D013006:Growth Hormone; D004262:DNA Restriction Enzymes; D013755:Tetradecanoylphorbol Acetate