PLAC1 expression increases during trophoblast differentiation: Evidence for regulatory interactions with the fibroblast growth factor-7 (FGF-7) axis

PLAC1 is a recently described, trophoblast-specific gene that localizes to a region of the X-chromosome important in placental development. Immunohistochemical analysis demonstrated that PLAC1 polypeptide localizes to the differentiated syncytiotrophoblast throughout gestation (8-41 weeks) as well as a small population of villous cytotrophoblasts. Consistent with these observations, quantitative RT-PCR demonstrated that PLAC1 mRNA increases more than 300-fold during cytotrophoblast differentiation in culture to form syncytiotrophoblasts. Agents known to be relevant to trophoblast differentiation were then tested for the ability to influence PLAC1 expression. Fibroblast growth factor-7 (FGF-7), also known as keratinocyte growth factor (KGF), stimulated PLAC1 mRNA expression approximately two-fold in the BeWo ^b30 trophoblast cell line. FGF-7 stimulation was significantly inhibited by PD-98059 and wortmannin suggesting mediation via MAP kinase and PI-3 kinase-dependent signaling pathways. Interestingly, epidermal growth factor (EGF) treatment of trophoblasts had no effect on PLAC1 expression alone, but potentiated the effect of FGF-7, suggesting the presence of a regulatory interaction of the two growth factors. FGF-7 and its receptor, FGFR-2b, exhibited spatial overlap with PLAC1 suggesting these regulatory interactions are physiologically relevant during gestation. These data demonstrate PLAC1 expression is upregulated during trophoblast differentiation, localizing primarily to the differentiated syncytiotrophoblast. Furthermore PLAC1 expression is specifically regulated by peptide growth factors relevant to trophoblast differentiation.