Placenta-specific protein 1 (PLAC1) is a small secreted protein expressed exclusively in trophoblast cells in the mammalian placenta. PLAC1 is expressed early in gestation and is maintained throughout. It is thought to function in trophoblast invasion of the uterine epithelium and, subsequently, to anchor the placenta to the epithelium. In recent years, evidence has accumulated that PLAC1 is also expressed in a variety of human solid tumors, notably in breast cancers. We demonstrate for the first time that PLAC1 is ubiquitously expressed in tumors originating in uterine epithelium. Further, we find that PLAC1 expression is significantly higher in the more advanced, more aggressive endometrial serous adenocarcinomas and carcinosarcomas relative to endometrioid adenocarcinomas by more than 6-fold and 16-fold, respectively. We also show that PLAC1 is simultaneously transcribed from two promoters but that, in all cases, the more distal P1 promoter dominates the more proximal P2 promoter. While the function of the two PLAC1 promoters and their regulation are as yet unknown, overall expression data suggest that PLAC1 may serve as a biomarker for endometrial cancer as well as a potential prognostic indicator. 1. Introduction Placenta-specific protein 1 (PLAC1), encoded on human chromosome Xq26, is a small (212 amino acid) secreted protein whose normal expression is almost exclusively limited to placental trophoblast cells [1, 2]. Comparative genomics reveals that PLAC1 evolved after the divergence of placental mammals (Eutheria) from marsupials (Metatheria) as there are homologs throughout the former but no evidence in either of the other mammalian subclasses Metatheria and Prototheria (egg laying mammals) [3]. Among all Eutheria so far studied, PLAC1 shows a well conserved signal peptide (residues 1–23), a very highly conserved transmembrane domain (TMD) (residues 20–50), and a highly conserved region in the extracellular domain homologous to the N-terminal subdomain of the zona pellucida ZP3 glycoprotein (residues 58–118) [4, 5]. Normal expression of the PLAC1 protein is limited to the apical villous surface of syncytiotrophoblasts suggesting that it is involved in anchoring the placenta to the endometrium and maintaining that contact throughout gestation [2]. Moreover, the ZP3-like extracellular domain suggests that strong protein binding interactions are likely [6], and evidence that PLAC1 and F-actin colocalize further supports this view [2]. In addition to the highly specific expression in normal placental development and maintenance, several studies
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