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 1st 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.
Abbreviations
BCL6 | = | B-cell lymphoma 6 |
Plk1 | = | Polo-like kinase 1 |
PARP | = | poly(ADP-ribose) polymerase |
siRNA | = | small interfering RNA |
CHX | = | cycloheximide |
CPC | = | chromosomal passenger complex |
PCM | = | pericentriolar material |
HIF 1α | = | hypoxia-inducible factor 1α |
H2O2 | = | hydrogen peroxide |
Disclosure of Potential Conflicts of Interest
The authors declare no conflicts of interest.
Acknowledgments
We thank Dr. Charles H. Graham, Queen's University at Kingston, for kindly providing us the cell line HTR-8/SVneo. We thank also Ms. Hannah Salecker for technical assistance