Effect of lysophosphatidylglycerol on several signaling molecules in OVCAR-3 human ovarian cancer cells: involvement of pertussis toxin-sensitive G-protein coupled receptor.
In this study, we observed that lysophosphatidylglycerol (LPG) stimulated intracellular calcium ([Ca(2+)](i)) increase in OVCAR-3 human ovarian cancer cells. LPG-stimulated [Ca(2+)](i) increase was inhibited by U-73122 but not by U-73343, suggesting that LPG stimulates calcium signaling via phospholipase C activation. Moreover, pertussis toxin (PTX) almost completely inhibited [Ca(2+)](i) increase by LPG, indicating the activation of PTX-sensitive G-proteins. LPG-induced [Ca(2+)](i) increase was only observed in OVCAR-3 ovarian cancer cells and SK-OV3 ovarian cancer cells among tested several cell types. LPG also induced extracellular signal-regulated kinase (ERK) and Akt phosphorylation in OVCAR-3 ovarian cancer cells. Pertussis toxin did not affect the LPG-induced activation of ERK and Akt phosphorylation. We also found that LPG failed to stimulate NF-kappaB-driven luciferase activity in exogenously LPA(1), LPA(2), or LPA(3)-transfected HepG2 cells. Taken together we suggest that LPG stimulates a membrane bound receptor which is different from well-known LPA receptors (LPA(1), LPA(2), and LPA(3)), resulting in at least two different signaling cascades; one involves a pertussis toxin-sensitive and phospholipase C-dependent [Ca(2+)](i) increase, and the other involves a pertussis toxin-insensitive activation of ERK and Akt in ovarian cancer cells.
Park
Kyoung Sun
KS
Medical Research Center for Cancer Molecular Therapy, Dong-A University, Busan, Republic of Korea.
Kim
Mi-Kyoung
MK
Im
Dong-Soon
DS
Bae
Yoe-Sik
YS
D020013:Calcium Signaling; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D037342:Pertussis Toxin / Q000378:metabolism*; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism*
D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; C026223:lysophosphatidylglycerol; D037342:Pertussis Toxin; D051058:Oncogene Protein v-akt; D048049:Extracellular Signal-Regulated MAP Kinases