title: Signal transduction responses to lysophosphatidic acid and sphingosine 1-phosphate in human prostate cancer cells.
abstract: BACKGROUND
  Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are lipid mediators that bind to G-protein-coupled receptors. In this study, signaling responses to 18:1 LPA and S1P were examined in parallel in three human prostate cancer cell lines: PC-3, Du145, and LNCaP.
  
  
  METHODS
  Receptor expression was assessed by RT-PCR, Northern blotting, and immunoblotting. Cellular responses to mediators were studied by proliferation assays, phosphoprotein immunoblotting, and phospholipid metabolism assays.
  
  
  RESULTS
  All cell lines express mRNA for both LPA and S1P receptors. PC-3 and Du145, but not LNCaP, proliferate in response to LPA and S1P. Epidermal growth factor (EGF), phorbol 12-myristate 13-acetate (PMA), LPA, and S1P induce activation of Erks in PC-3 and Du145; only EGF and PMA activate Erks in LNCaP. In Du145 and PC-3, Akt is activated by EGF, LPA, and S1P. Akt is constitutively active in LNCaP; EGF but not LPA or S1P stimulates further phosphorylation. FAK is phosphorylated in response to both LPA and S1P in PC-3 and Du145, but not in LNCaP. LPA and S1P stimulate phospholipase D (PLD) activity to varying extents in the different cell lines. Notably, both lipid mediators activate PLD in LNCaP. In Du145, LPA, but not S1P, activates PLD and enhances cellular production of LPA.
  
  
  CONCLUSIONS
  Although both LPA and S1P induce signal transduction in all prostate cancer cell lines studied, a proliferation response is observed only when the Erk, Akt, and FAK pathways are activated. Other responses to the lipid mediators, such as PLD activation, likely contribute to other cellular outcomes.
authors.affiliation: Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Terra C
authors.initials: TC
authors.lastname: Gibbs
authors.forename: Maria V
authors.initials: MV
authors.lastname: Rubio
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yuhuan
authors.initials: Y
authors.lastname: Xie
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Kipp
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Meier
mesh_terms: D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007536:Isomerism; D008246:Lysophospholipids / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000081025:Sphingosine-1-Phosphate Receptors; D014443:Tyrosine / Q000378:metabolism
chemical_list: D016895:Culture Media, Serum-Free; D008246:Lysophospholipids; D012333:RNA, Messenger; D049368:Receptors, Lysophosphatidic Acid; D049349:Receptors, Lysosphingolipid; C477362:S1PR1 protein, human; D000081025:Sphingosine-1-Phosphate Receptors; C060506:sphingosine 1-phosphate; D014443:Tyrosine; D013110:Sphingosine; C032881:lysophosphatidic acid