Prostasin regulates human placental trophoblast cell proliferation via the epidermal growth factor receptor signaling pathway

    Authors

    Y. Y. Fu; W. L. Gao; M. Q. Chen; K. X. Chai; Y. L. Wang;L. M. Chen

    Comments

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    Abbreviated Journal Title

    Hum. Reprod.

    Keywords

    prostasin; trophoblast; cell proliferation; epidermal growth factor; receptor-mitogen-activated protein kinase signaling; SERINE-PROTEASE; SODIUM-CHANNEL; EXPRESSION; EGFR; CANCER; LINE; INVASIVENESS; RETARDATION; PREGNANCIES; ACTIVATION; Obstetrics & Gynecology; Reproductive Biology

    Abstract

    Prostasin is a glycosylphosphatidylinositol-anchored extracellular serine protease with a role in epidermal growth factor receptor (EGFR) signal modulation. EGFR signaling has been shown to be important for regulating cytotrophoblast (CT) cell proliferation in human placenta. We investigated the impact of prostasin expression regulation on this cellular function as well as the molecular mechanisms involved in human cytotrophoblastic cells. An immortalized normal human CT cell line (B6Tert-1) was used as an in vitro cell model. Prostasin expression in B6Tert-1 cells was knocked down by transfection of a short interfering RNA. Lentivirus-mediated expression of recombinant human prostasin under tetracycline regulation was performed to obtain stable B6Tert-1 cell sublines that over-expressed prostasin. Changes in cell proliferation and EGFR signaling were evaluated by immunocytochemistry for Ki67 and western blot analysis, respectively, in B6Tert-1 cells with knocked-down or increased prostasin expression. Prostasin knock-down in B6Tert-1 cells resulted in inhibition of cell proliferation, in association with down-regulated EGFR protein expression (both P < 0.05 versus control) as well as reduced phosphorylation of c-raf, mitogen-activated protein kinase (MAPK) kinases (MEK1/2) and extracellular signal-regulated kinases (Erk1/2) (all P < 0.05 versus control). Over-expression of prostasin led to up-regulation of the EGFR protein, but had no effect on cell proliferation or phosphorylation of MAPK signaling molecules in the B6Tert-1 cells. Prostasin may regulate trophoblast cell proliferation via modulating the EGFR-MAPK signaling pathway.

    Journal Title

    Human Reproduction

    Volume

    25

    Issue/Number

    3

    Publication Date

    1-1-2010

    Document Type

    Article

    Language

    English

    First Page

    623

    Last Page

    632

    WOS Identifier

    WOS:000274490700011

    ISSN

    0268-1161

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