title: Transcriptional and posttranscriptional mechanisms in epidermal growth factor regulation of human chorionic gonadotropin (hCG) subunits and hCG receptor gene expression in human choriocarcinoma cells.
abstract: Epidermal growth factor (EGF) stimulates the secretion of hCG in choriocarcinoma cells. However, the molecular mechanisms involved in this EGF action have never previously been investigated. The present study investigated them as well as EGF regulation of the hCG/LH (LH) receptor gene in JEG-3 human choriocarcinoma cells. The JEG-3 cells contain multiple EGF receptor messenger RNA (mRNA) transcripts and a single 170-kilodalton immunoreactive receptor protein. The human EGF can bind to the receptor protein and stimulate the receptor autophosphorylation as well as the phosphorylation of four other membrane proteins. Culturing JEG-3 cells with recombinant human EGF resulted in a dose- and time-dependent increase in hCG secretion. The maximal effect was seen at 100 ng/ml EGF, with a time lag of about 5 h. Tyrosine kinase, but not protein kinase-C or protein kinase-A, signaling was involved in the EGF action to increase hCG secretion. The EGF-induced increase in hCG secretion was not due to an increase in cell number or differentiation into multinuclear syncytia. EGF treatment resulted in a dose- and time-dependent increase in steady state levels of hCG alpha and hCG beta mRNAs. This increase was due to the stabilization of subunit mRNA transcripts. The increase in subunit mRNAs preceded the increase in hCG secretion. The EGF treatment resulted in a dose- and time-dependent decrease in steady state levels of the hCG/LH receptor mRNA transcripts. The decrease was due to a transcriptional inhibition of receptor gene. EGF treatment paradoxically stabilized hCG/LH receptor protein. In summary, EGF treatment up-regulates hCG subunits gene expression and down-regulates hCG/LH receptor mRNAs involving transcriptional and posttranscriptional mechanisms in JEG-3 human choriocarcinoma cells.
authors.affiliation: Department of Obstetrics and Gynecology, University of Louisville School of Medicine, Kentucky 40292.
authors.forename: H
authors.initials: H
authors.lastname: Cao
authors.forename: Z M
authors.initials: ZM
authors.lastname: Lei
authors.forename: C V
authors.initials: CV
authors.lastname: Rao
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000235:genetics / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006706:Homeostasis; D006801:Humans; D002820:Hydatidiform Mole, Invasive / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008934:Mitogens / Q000494:pharmacology; D011247:Pregnancy; D047428:Protein Kinase Inhibitors; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D011974:Receptors, LH / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
chemical_list: D006063:Chorionic Gonadotropin; D008934:Mitogens; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D011974:Receptors, LH; D004815:Epidermal Growth Factor; D066246:ErbB Receptors