Plac1, a placenta-specific gene, is expressed exclusively by cells of trophoblastic lineage in the mouse, and maps to a region of the X chromosome known to be important in placental growth. These studies were undertaken to define the cellular location of the mRNA for the human orthologue, PLAC1, within the human placenta, and to examine its expression throughout gestation. By Northern analysis, PLAC1 mRNA was detected in term human placenta, migrating as a single 1.7 kb transcript, but in no other fetal or adult tissues tested. Expression was observed throughout gestation, whereas mouse Plac1 is significantly reduced after 12.5 dpc. Using an (35)S-labeled riboprobe, PLAC1 expression was trophoblast-specific at all stages of gestation (8-41 weeks); no expression was seen in cells within the stromal compartment or decidua. Using BeWo choriocarcinoma cells as a trophoblast model, keratinocyte growth factor (KGF) stimulated steady-state PLAC1 mRNA expression approximately twofold by Northern analysis and quantitative real-time PCR. Stimulation was observed only after 24 hr of exposure, suggesting that the stimulatory effect of KGF is secondary to the promotion of trophoblast growth or differentiation. No change in mRNA levels resulted from exposure to insulin-like growth factor II (IGF-II). Trophoblast-specific expression throughout gestation and responsiveness to KGF are consistent with a fundamental role for PLAC1 at the maternal-fetal interface.