title: Crucial cross-talk of interleukin-1β and progesterone in human choriocarcinoma.
abstract: Choriocarcinoma is a highly malignant epithelial tumour that is most often associated with hydatidiform mole and presents the most common emergency medical problem in the management of trophoblast disease. We hypothesise that the hormones/cytokines present within the tumour microenvironment play key roles in the development of choriocarcinoma. In this study we assessed the effects of interleukin-1β (IL-1β) on cell death in the presence or absence of the sex hormone progesterone using two choriocarcinoma cell lines (BeWo and JEG-3) as in vitro experimental models. Although IL-1β induced cell death in both cell lines, the effect was more pronounced in JEG-3 cells, where cell death reached 40% compared to 15% in BeWo cells. Cell death of JEG-3 cells in response to IL-1β was significantly decreased by co-treatment with 100 nM and 1000 nM progesterone and completely abolished at a progesterone concentration of 1000 nM. Progesterone was also able to induce phosphorylation of ERK1/2 in these cells. Pretreatment of JEG-3 cells with a specific MAPK inhibitor (UO126) inhibited progesterone's inhibitory effect on cell death. Collectively, these data provide evidence of cross-talk between progesterone and IL-1β in this aggressive and poorly understood tumour that involves activation of a MAPK pathway and involvement of numerous progesterone receptors.
authors.affiliation: Centre for Cell Chromosome Biology, Biosciences, Centre for Cell                     and Chromosome Biology, School of Health Sciences and Social Care, Brunel                     University, Uxbridge, UB8 3PH, UK.
authors.forename: Elena
authors.initials: E
authors.lastname: Zachariades
authors.forename: Dionisis
authors.initials: D
authors.lastname: Mparmpakas
authors.forename: Peter
authors.initials: P
authors.lastname: Thomas
authors.forename: Mariann
authors.initials: M
authors.lastname: Rand-Weaver
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Karteris
mesh_terms: D002070:Butadienes / Q000494:pharmacology; D016923:Cell Death; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D008565:Membrane Proteins / Q000819:agonists / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism*; D011397:Promegestone / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000819:agonists / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D059016:Tumor Microenvironment; D014594:Uterine Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D002070:Butadienes; D053583:Interleukin-1beta; D008565:Membrane Proteins; D009570:Nitriles; C115296:PGRMC1 protein, human; D047428:Protein Kinase Inhibitors; D011980:Receptors, Progesterone; C113580:U 0126; D011374:Progesterone; D011397:Promegestone; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3