title: Placental lactogen-I gene activation in differentiating trophoblast cells: extrinsic and intrinsic regulation involving mitogen-activated protein kinase signaling pathways.
abstract: Trophoblast giant cells are one of the primary endocrine cell types of the rodent placenta. Placental lactogen-I (PL-I) is the initial prolactin (PRL) family member expressed as trophoblast giant cells differentiate. In this report, we use the Rcho-1 trophoblast cell line as a model for studying the regulation of PL-I gene expression during trophoblast giant cell differentiation. Evidence is provided for trophoblast cell expression of epidermal growth factor receptor (EGFR), ErbB2, fibroblast growth factor receptor 1 (FGFR1), transforming growth factor-alpha, and heparin-binding EGF. EGF and FGF-2 stimulated PL-I mRNA and protein accumulation and PL-I promoter activity in a concentration-dependent manner. These latter growth factor actions on PL-I promoter activities were specifically inhibited by cotransfection with dominant negative constructs for EGFR and FGFRs respectively. Utilization of the mitogen-activated protein kinase (MAPK) pathway by EGF and FGF-2 in trophoblast cells was demonstrated by growth factor stimulation of a Gal4 DNA binding/Elk1 transactivational domain fusion construct, and more specifically by activation of extracellular signal regulated kinase and p38 MAPK. PL-I gene activation was also sensitive to disruption of MAPK and activation protein-1 (AP-1) signaling pathways. In conclusion, autocrine/paracrine pathways involving EGFR and FGFR1, MAPK and AP-1 are shown to participate in the regulation of the PL-I gene in differentiating trophoblast cells.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Peters
authors.forename: B M
authors.initials: BM
authors.lastname: Chapman
authors.forename: M W
authors.initials: MW
authors.lastname: Wolfe
authors.forename: M J
authors.initials: MJ
authors.lastname: Soares
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology*; D015726:Giant Cells / Q000378:metabolism*; D006133:Growth Substances / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D010928:Placental Lactogen / Q000235:genetics*; D011247:Pregnancy; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015533:Transcriptional Activation; D016211:Transforming Growth Factor alpha / Q000378:metabolism
chemical_list: D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D016222:Fibroblast Growth Factor 2; D006133:Growth Substances; D010928:Placental Lactogen; D018719:Erb-b2 Receptor Tyrosine Kinases; D017468:Receptors, Fibroblast Growth Factor; D016211:Transforming Growth Factor alpha