Regulation of lactoferrin gene expression by estrogen and epidermal growth factor: molecular mechanism.
Lactoferrin (LF) is a member of the transferrin gene family. Its expression in the mouse uterus is regulated by estrogen and epidermal growth factor (EGF). The author et al. cloned the LF gene promoter/enhancer region, and demonstrated that multihormone signaling pathways are involved in modulating LF gene activity. Three short but complex modules, within 400 bp from the transcription initiation site of the mouse LF gene, contain the response elements that are responsible for estrogen, retinoic acid, mitogen, and growth factor stimulation. These elements have been identified and characterized, using reporter constructs transiently transfected into human endometrial carcinoma RL95-2 cells. The author et al. used molecular approaches, such as deletion, insertion, and site-directed mutagenesis, to determine the relationship between the response elements, and to fine-map the crucial nucleotides within them. This article reviews the characterization of the estrogen and EGF response elements of the mouse LF gene promoter.
Teng
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Gene Regulation Group, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Teng@niehs.nih.gov
D000818:Animals; D001483:Base Sequence; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000502:physiology*; D004967:Estrogens / Q000235:genetics / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007781:Lactoferrin / Q000235:genetics*; D051379:Mice; D008954:Models, Biological; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D014599:Uterus / Q000378:metabolism
D004967:Estrogens; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D007781:Lactoferrin