title: The EGF response element in the prolactin promoter.
abstract: Epidermal growth factor (EGF) increases prolactin gene expression in GH4 cells, but the promoter element(s) required for this response has not been clearly defined. We identified a bipartite element - 96/ - 87, - 76/ - 67 in the rat proximal promoter that is essential for EGF signaling using deletion and linker-scanning mutants of the prolactin promoter. This element was active in either normal or inverted orientation when transferred to a heterologous promoter (mammary-tumor virus). We had previously identified this element as the cAMP/insulin response element of the prolactin promoter. However, the effects of EGF are additive with the responses to insulin or cAMP implying that EGF activated prolactin gene transcription by a mechanism different from insulin or cAMP. The EGF response element of the prolactin promoter is a recognition sequence for the Ets-related family of transcription factors and Ets-related factors have been shown to bind this element. Expression of the DNA-binding domain of c-Ets-1, which acts as a dominant negative inhibitor of Ets-related transcription factors, reduces EGF-increased prolactin-CAT expression 65% in GH4 cells. Thus, both EGF and insulin may signal through Ets-related transcription factors to activate prolactin gene transcription at the same response element in the prolactin proximal promoter.
authors.affiliation: Department of Medicine, New York University Medical Center, NY 10016, USA.
authors.forename: K K
authors.initials: KK
authors.lastname: Jacob
authors.forename: E
authors.initials: E
authors.lastname: Wininger
authors.forename: K
authors.initials: K
authors.lastname: DiMinni
authors.forename: F M
authors.initials: FM
authors.lastname: Stanley
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005786:Gene Expression Regulation; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008969:Molecular Sequence Data; D011388:Prolactin / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D004815:Epidermal Growth Factor; D011388:Prolactin; D000242:Cyclic AMP