Expression of multiple membrane-associated phospholipase A1 beta transcript variants and lysophosphatidic acid receptors in Ewing tumor cells.
The prognosis for patients with advanced stages of Ewing family tumors (EFT) is very poor. EFT express high levels of phosphatidic acid specific membrane-associated phospholipase A1 beta (lipase I, LIPI). LIPI is a cancer/testis antigen and the high tumor specificity suggests that LIPI might be an attractive target for new diagnostic and/or therapeutic developments. By using reverse transcriptase-polymerase chain reaction (RT-PCR), we observed simultaneous presence of multiple LIPI transcript variants in EFT. We cloned and sequenced these transcript variants from EFT cell lines. Sequence analysis indicated that all transcript variants were derived by alternative splicing. Homology modeling of corresponding protein structures suggested that different transcript variants differ in their regulatory lid domains. In addition, expression of receptors for lysophosphatidic acid (LPA) was analyzed in a panel of EFT cell lines by RT-PCR. We observed that EFT cell lines expressed high levels of LPA receptors. Different LIPI transcript variants present in EFT might be involved in the pathogenesis of EFT by signaling via these LPA receptors.
Department of Pediatrics, Martin-Luther-University Halle-Wittenberg, Ernst Grube Str. 40, 06097 Halle, Germany.
Benjamin Joachim
BJ
Schmiedel
Christoph
C
Hutter
Manuela
M
Hesse
Martin Sebastian
MS
Staege
D017398:Alternative Splicing / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000235:genetics*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000201:enzymology*; D005091:Exons / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D054466:Phospholipases A1 / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics* / Q000378:metabolism; D012512:Sarcoma, Ewing / Q000201:enzymology* / Q000235:genetics*; D040681:Structural Homology, Protein
D000951:Antigens, Neoplasm; C504173:LIPC protein, human; D022821:RNA Splice Sites; D012333:RNA, Messenger; D049368:Receptors, Lysophosphatidic Acid; D008049:Lipase; C568778:LIPI protein, human; D054466:Phospholipases A1