title: B-cell lymphoma 6 promotes proliferation and survival of trophoblastic cells.
abstract: Preeclampsia is one of the leading causes of maternal and perinatal mortality and morbidity and its pathogenesis is not fully understood. B-cell lymphoma 6 (BCL6), a key regulator of B-lymphocyte development, is altered in preeclamptic placentas. We show here that BCL6 is present in all 3 studied trophoblast cell lines and it is predominantly expressed in trophoblastic HTR-8/SVneo cells derived from a 1(st) trimester placenta, suggestive of its involvement in trophoblast expansion in the early stage of placental development. BCL6 is strongly stabilized upon stress stimulation. Inhibition of BCL6, by administrating either small interfering RNA or a specific small molecule inhibitor 79-6, reduces proliferation and induces apoptosis in trophoblastic cells. Intriguingly, depletion of BCL6 in HTR-8/SVneo cells results in a mitotic arrest associated with mitotic defects in centrosome integrity, indicative of its involvement in mitotic progression. Thus, like in haematopoietic cells and breast cancer cells, BCL6 promotes proliferation and facilitates survival of trophoblasts under stress situation. Further studies are required to decipher its molecular roles in differentiation, migration and the fusion process of trophoblasts. Whether increased BCL6 observed in preeclamptic placentas is one of the causes or the consequences of preeclampsia warrants further investigations in vivo and in vitro.
authors.affiliation: a Department of Gynecology and Obstetrics , School of Medicine, J. W. Goethe-University , Frankfurt, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Muschol-Steinmetz
authors.affiliation: a Department of Gynecology and Obstetrics , School of Medicine, J. W. Goethe-University , Frankfurt, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Jasmer
authors.affiliation: a Department of Gynecology and Obstetrics , School of Medicine, J. W. Goethe-University , Frankfurt, Germany.
authors.forename: Nina-Naomi
authors.initials: NN
authors.lastname: Kreis
authors.affiliation: a Department of Gynecology and Obstetrics , School of Medicine, J. W. Goethe-University , Frankfurt, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Steinhäuser
authors.affiliation: a Department of Gynecology and Obstetrics , School of Medicine, J. W. Goethe-University , Frankfurt, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ritter
authors.affiliation: b Department of Pediatric Surgery and Pediatric Urology , School of Medicine, J. W. Goethe-University , Frankfurt , Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Rolle
authors.affiliation: a Department of Gynecology and Obstetrics , School of Medicine, J. W. Goethe-University , Frankfurt, Germany.
authors.forename: Juping
authors.initials: J
authors.lastname: Yuan
authors.affiliation: a Department of Gynecology and Obstetrics , School of Medicine, J. W. Goethe-University , Frankfurt, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Louwen
mesh_terms: D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D059447:Cell Cycle Checkpoints; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008938:Mitosis; D011225:Pre-Eclampsia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014327:Trophoblasts / Q000378:metabolism* / Q000473:pathology
chemical_list: C084103:BCL6 protein, human; D051560:Proto-Oncogene Proteins c-bcl-6; D034741:RNA, Small Interfering
keywords: BCL6; centrosome fragmentation; preeclampsia; proliferation; survival; trophoblast