EXPRESSION AND TRANSCRIPTIONAL REGULATION OF THE PD-I-ALPHA AUTOTAXINGENE IN NEUROBLASTOMA/

Autotaxin (ATX) is a newly found autocrine tumor cell motility-stimula ting factor. ATX is a member of the ecto-phosphodiesterase I (PD-I)/nu cleotide pyrophosphatase family. PD-I alpha was found as a brain-type ecto-phosphodiesterase I/nucleotide pyrophosphatase. ATX and PD-I alph a are alternative splicing products from one gene. ATX stimulates moti lity of A2058 melanoma cells in vitro; however, it has not been known if PD-I alpha/ATX is expressed in naturally occurred human tumors. In this study, we examined the expression of the human PD-I alpha/ATX gen e in human neuroblastoma tumor tissues and the motility stimulating ac tivity of recombinant ATX on neuroblastoma cells and investigated its transcriptional regulatory mechanism in a human neuroblastoma cell lin e. The PD-I alpha/ATX gene was expressed in the primary tumor tissues from neuroblastoma patients to varying degrees. This gene is also expr essed in the SMS-KAN neuroblastoma cell line. We identified both isofo rms, PD-I alpha and ATX, in these tumor tissues and SMS-KAN cells. The recombinant ATX stimulated the motility of SMS-KAN cells at low nanom olar concentration. We situated the promoter region, which is essentia l for its transcription in SMS-KAN cells, at -287 to -251 nucleotides by the promoter activity assay. The gel-shift assay revealed that ther e exists a nuclear protein in SMS-KAN cells that binds this region. Th ese new insights about autocrine tumor cell motility-stimulating prote in will help us to understand the metastatic mechanism of human neurob lastoma.