Anti-CD15 monoclonal antibody, clone NDT-2

Trophoblast invasion is crucial for embryo implantation and successful pregnancy. Urokinase-type plasminogen activator (uPA)/urokinase-type plasminogen activator receptor (uPAR) are expressed on trophoblasts and involved in trophoblast invasion. The transcription factor activator protein 1 (AP1) (c-Fos and cJun) and fucosyltransferase IV (FUT4) have been found to be involved in this process. However, the relationship of uPA/uPAR, AP1 and FUT4 is unclear. The current study aimed to investigate the role of AP1 in uPA/uPAR induced FUT4 expression and trophoblast invasion. We found that p-c-Fos and p-c-Jun were decreased in abortion patients compared to that in normal pregnant women. Employing human trophoblastic cells, we then demonstrated that uPA/uPAR induced the expression of p-c-Fos and p-c-Jun. Applying an electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP), we further proved that transcription factor AP1 bound to FUT4 promoter that could increase FUT4 transcriptional activity, further promoting trophoblast cell migration and invasion through JNK MAPK signaling pathway. Taken together, these results suggest that uPA/uPAR induces FUT4 expression, and trophoblast cell invasion mediated by AP1 transcription factor (c-Fos and c-Jun). Our findings provide novel insights into the relationship between AP1 and abortion.

In fucosyltransferase genes, mRNA expression is regulated in a cell-type-specific manner. The expression level of human fucosyltransferase 4 (FUT4) mRNA is high in both colon adenocarcinoma and myeloid cell lines. We will demonstrate here cell-specific expression and transcriptional regulation of the FUT4 gene. FUT4 has two different transcription initiation sites that respectively produce long- and short-form mRNAs. To determine the major FUT4 transcript in colon adenocarcinoma and myeloid cell lines, we analyzed the transcriptional starting sites of the FUT4 gene in myeloid and colon adenocarcinoma cell lines, using 5'-RACE, RT-PCR, and luciferase analysis. The results suggested that the expression level of short-form mRNA is higher than the long-farm transcript in the colon adenocarcinoma cell lines and that the expression level of long-form mRNA is higher than the short-form transcript in the myeloid cell lines. Using a luciferase assay, we identified a functional DNA portion within FUT4 genomic DNA that confers a colon adenocarcinoma cell line-specific enhancer, located in nucleotide number (nt) -256 to -44, and a myeloid cell line-specific enhancer, located in nt -686 to -582. The present results suggest that these elements play a critical role in the colon adenocarcinoma and leukemia cell-specific transcriptional regulation of the FUT4 gene. (C) 2000 Academic Press.