title: Prostaglandin E2 promotes liver cancer cell growth by the upregulation             of FUSE-binding protein 1 expression.
abstract: Liver cancer is a common human cancer with a high mortality rate and currently there is no effective chemoprevention or systematic treatment. Recent evidence suggests that prostaglandin E(2) (PGE(2)) plays an important role in the occurrence and development of liver cancer. However, the mechanisms through which PGE(2) promotes liver cancer cell growth are not yet fully understood. It has been reported that the increased expression of FUSE-binding protein 1 (FBP1) significantly induces the proliferation of liver cancer cells. In this study, we report that PGE(2) promotes liver cancer cell growth by the upregulation of FBP1 protein expression. Treatment with PGE2 and the E prostanoid 3 (EP3) receptor agonist, sulprostone, resulted in the time-dependent increase in FBP1 protein expression; sulprostone increased the viability of the liver cancer cells. The protein kinase A (PKA) inhibitor, H89, and the adenylate cyclase (AC) inhibitor, SQ22536, inhibited the cell viability accelerated by sulprostone. By contrast, the Gi subunit inhibitor, pertussis toxin (PTX), exhibited no significant effect. Treatment with PGE(2) and sulprostone caused a decrease in JTV1 protein expression, blocked the binding of JTV1 with FBP1, which served as a mechanism for FBP1 degradation, leading to the decreased ubiquitination of FBP1 and the increase in FBP1 protein expression. Furthermore, H89 and SQ22536 prevented the above effects of JTV1 and FBP1 induced by PGE(2) and sulprostone. These findings indicate that the EP3 receptor activated by PGE(2) may couple to Gs protein and activate cyclic AMP (cAMP)-PKA, downregulating the levels of JTV1 protein, consequently inhibiting the ubiquitination of FBP1 and increasing FBP1 protein expression, thus promoting liver cancer cell growth. These observations provide new insights into the mechanisms through which PGE(2) promotes cancer cell growth.
authors: Cancer Center, Department of Pathology, Nanjing Medical University,                     Nanjing 210029, P.R. China.
authors: Juan
authors: J
authors: Ma
authors: Meng
authors: M
authors: Chen
authors: Shu-Kai
authors: SK
authors: Xia
authors: Wei
authors: W
authors: Shu
authors: Yan
authors: Y
authors: Guo
authors: Yao-Hui
authors: YH
authors: Wang
authors: Yan
authors: Y
authors: Xu
authors: Xiao-Ming
authors: XM
authors: Bai
authors: Li
authors: L
authors: Zhang
authors: Hai
authors: H
authors: Zhang
authors: Min
authors: M
authors: Zhang
authors: Yi-Pin
authors: YP
authors: Wang
authors: Jing
authors: J
authors: Leng
mesh_terms: D000020:Abortifacient Agents, Nonsteroidal / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004265:DNA Helicases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008113:Liver Neoplasms / Q000378:metabolism*; D009687:Nuclear Proteins; D037342:Pertussis Toxin / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051899:Smad2 Protein / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D054875:Ubiquitination
chemical_list: C575685:AIMP2 protein, human; D000020:Abortifacient Agents, Nonsteroidal; D000067956:Adenylyl Cyclase Inhibitors; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C492258:FUBP1 protein, human; D007546:Isoquinolines; D009687:Nuclear Proteins; C545647:PTGER3 protein, human; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D013449:Sulfonamides; C017759:9-(tetrahydro-2-furyl)-adenine; D005576:Colforsin; C016767:sulprostone; D000242:Cyclic AMP; D037342:Pertussis Toxin; D004265:DNA Helicases; D000225:Adenine; D015232:Dinoprostone; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide