Title | S1P/S1P2 signaling induces cyclooxygenase-2 expression in Wilms tumor. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Li M-H, Sanchez T, Milne GL, Morrow JD, Hla T, Ferrer F |
Journal | J Urol |
Volume | 181 |
Issue | 3 |
Pagination | 1347-52 |
Date Published | 2009 Mar |
ISSN | 1527-3792 |
Keywords | Cyclooxygenase 2, Humans, Kidney Neoplasms, Receptors, Lysosphingolipid, Signal Transduction, Sphingosine-1-Phosphate Receptors, Tumor Cells, Cultured, Wilms Tumor |
Abstract | PURPOSE: Cyclooxygenase-2 has been reported to be ubiquitously expressed in Wilms tumor, the most common malignant renal tumor in children. However, to our knowledge the regulation mechanism of cyclooxygenase-2 expression remains unexplored. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction and Western blot were performed to detect cyclooxygenase-2 mRNA and protein expression in WiT49 cells upon stimulation by S1P (Biomol(R)), and S1P(2) and cyclooxygenase-2 mRNA expression in 10 freshly frozen Wilms tumor tissues and matched normal tissues. Over expression, blockade and down-regulation of S1P(2) were determined using adenoviral transduction, the S1P(2) antagonist JTE-013 (Tocris Bioscience, Ellisville, Missouri) and small interfering RNA (Dharmacon, Lafayette, Colorado) transfection, respectively. The prostaglandin E(2) level in WiT49 cells was determined by gas chromatography/mass spectrometry. RESULTS: S1P induced cyclooxygenase-2 mRNA and protein expression in WiT49 cells in a concentration dependent manner. Over expression of S1P(2) in WiT49 cells led to a significant increase in cyclooxygenase-2 mRNA and protein expression as well as subsequent prostaglandin E(2) synthesis. In addition, pretreatment of those cells that over expressed S1P(2) with the S1P(2) selective antagonist JTE-013 completely blocked S1P induced cyclooxygenase-2 protein expression. In accordance with these results silencing S1P(2) in WiT49 cells down-regulated S1P induced cyclooxygenase-2 expression. Further research in 10 Wilms tumor specimens showed that S1P(2) mRNA is greatly increased in Wilms tumor. CONCLUSIONS: S1P induced cyclooxygenase-2 expression in Wilms tumor and this effect was mediated by S1P(2). This finding extends the biological function of S1P(2) and provides the biochemical basis for developing inhibitors targeting the S1P/cyclooxygenase-2 signaling pathway. |
DOI | 10.1016/j.juro.2008.10.140 |
Alternate Journal | J Urol |
PubMed ID | 19157443 |
PubMed Central ID | PMC4132875 |
Grant List | GM15431 / GM / NIGMS NIH HHS / United States K08 DK070468 / DK / NIDDK NIH HHS / United States R01 DK048831 / DK / NIDDK NIH HHS / United States P50 GM015431 / GM / NIGMS NIH HHS / United States ES13125 / ES / NIEHS NIH HHS / United States K08DK070468A / DK / NIDDK NIH HHS / United States P01 ES013125 / ES / NIEHS NIH HHS / United States DK48831 / DK / NIDDK NIH HHS / United States R01 CA168903 / CA / NCI NIH HHS / United States P01 GM015431 / GM / NIGMS NIH HHS / United States |
Related Faculty:
Teresa Sanchez, Ph.D.