4.6 Article

PIM kinases 1, 2 and 3 in intracellular LIF signaling, proliferation and apoptosis in trophoblastic cells

期刊

EXPERIMENTAL CELL RESEARCH
卷 359, 期 1, 页码 275-283

出版社

ELSEVIER INC
DOI: 10.1016/j.yexcr.2017.07.019

关键词

PIM kinases; Trophoblast; Placenta; Intracellular signaling; Reproduction

资金

  1. Siemens-DAAD Post Graduate Program [A/11/72004]
  2. German Academic Exchange Service (DAAD) [A/09/97227]
  3. local Interdisciplinary Center for Clinical Studies (IZKF Jena) [J54]
  4. Republic of Yemen
  5. German Research Society [M02017/3-1, M02017/3-2, MA1550/12-1]
  6. FAPESP, Brazil [11/22429-3, 14/23517-1]
  7. Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [11/22429-3, 14/23517-1] Funding Source: FAPESP

向作者/读者索取更多资源

Proviral insertion in murine (PIM) lymphoma proteins are mainly regulated by the Janus Kinase/Signal Transducer Activator of Transcription (JAK/STAT) signaling pathway, which can be activated by members of the Interleukin-6 (IL-6) family, including Leukemia Inhibitory Factor (LIF). Aim of the study was to compare PIM1, PIM2 and PIM3 expression and potential cellular functions in human first and third trimester trophoblast cells, the immortalized first trimester extravillous trophoblast cell line HTR8/SVneo and the choriocarcinoma cell line JEG-3. Expression was analyzed by qPCR and immunochemical staining. Functions were evaluated by PIM inhibition followed by analysis of kinetics of cell viability as assessed by MTS assay, proliferation by BrdU assay, and apoptosis by Western blotting for BAD, BCL-XL, (cleaved) PARP, CASP3 and c-MYC. Apoptosis and necrosis were tested by flow cytometry (annexin V/propidium iodide staining). All analyzed PIM kinases are expressed in primary trophoblast cells and both cell lines and are regulated upon stimulation with LIF. Inhibition of PIM kinases significantly reduces viability and proliferation and induces apoptosis. Simultaneously, phosphorylation of c-MYC was reduced. These results demonstrate the involvement of PIM kinases in LIF-induced regulation in different trophoblastic cell lines which may indicate similar functions in primary cells.

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