Lysophosphatidic acid transactivates both c-Met and epidermal growth factor receptor, and induces cyclooxygenase-2 expression in human colon cancer LoVo cells.
OBJECTIVE
To examine whether lysophosphatidic acid (LPA) induces phosphorylation of c-Met and epidermal growth factor receptor (EGFR), both of which have been proposed as prognostic markers of colorectal cancer, and whether LPA induces cyclooxygenase-2 (COX-2) expression in human colon cancer cells.


METHODS
Using a human colon cancer cell line, LoVo cells, we performed immunoprecipitation analysis, followed by Western blot analysis. We also examined whether LPA induced COX-2 expression, by Western blot analysis.


RESULTS
Immunoprecipitation analysis revealed that 10 micromol/L LPA induced tyrosine phosphorylation of c-Met and EGFR in LoVo cells within a few minutes. We found that c-Met tyrosine phosphorylation induced by LPA was not attenuated by pertussis toxin or a matrix metalloproteinase inhibitor, in marked contrast to the results for EGFR. In addition, 0.2-40 micromol/L LPA induced COX-2 expression in a dose-dependent manner.


CONCLUSIONS
Our results suggest that LPA acts upstream of various receptor tyrosine kinases (RTKs) and COX-2, and thus may act as a potent stimulator of colorectal cancer.
Shida
Dai
D
Department of Surgical Oncology, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Japan. dshida-tky@umin.ac.jp
Kitayama
Joji
J
Yamaguchi
Hironori
H
Yamashita
Hiroharu
H
Mori
Ken
K
Watanabe
Toshiaki
T
Nagawa
Hirokazu
H
D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D009578:Nitrobenzenes / Q000378:metabolism; D010766:Phosphorylation; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D015398:Signal Transduction; D013449:Sulfonamides / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D008246:Lysophospholipids; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met; C032881:lysophosphatidic acid