title: Mitogen-activated protein kinase pathway is involved in androgen-independent PSA gene expression in LNCaP cells.
abstract: BACKGROUND
  Prostate specific antigen (PSA) is regulated by growth factors and hormones through functional androgen responsive elements in the promoter region of the PSA gene. However, the molecular basis for androgen independent PSA elevation in hormone refractory prostate cancer is unknown. The purpose of this study was to investigate the role of MAP kinase activation in androgen independent regulation of PSA expression.
  
  
  METHODS
  LNCaP cells transfected with MEK1 expression vector with or without the MAP kinase inhibitor U0126 under low androgen conditions were analyzed by luciferase assay and electrophoretic mobility shift assay (EMSA).
  
  
  RESULTS
  Transfection experiments of the proximal PSA promoter linked to Luc-reporter identified one region designated as "B" motif centered at -60 bp to be essential for basal activation. Co-transfection with the MEK1 activated vector enhanced PSA expression, while mutation of the "B" motif totally abrogated this induction. EMSA showed a specific DNA-protein complex, but Sp1 family members and AR do not interact with the "B" region by supershift analysis.
  
  
  CONCLUSIONS
  Our data suggest that enhanced androgen-independent PSA gene expression in MAP kinase-induced LNCaP cells is mediated, at least in part, by the "B" motif of the PSA promoter.
authors.affiliation: Department of Urology, Mie University School of Medicine, Tsu, Mie, Japan.
authors.forename: Omar E
authors.initials: OE
authors.lastname: Franco
authors.forename: Takehisa
authors.initials: T
authors.lastname: Onishi
authors.forename: Kensuke
authors.initials: K
authors.lastname: Yamakawa
authors.forename: Kiminobu
authors.initials: K
authors.lastname: Arima
authors.forename: Makoto
authors.initials: M
authors.lastname: Yanagawa
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sugimura
authors.forename: Juichi
authors.initials: J
authors.lastname: Kawamura
mesh_terms: D000728:Androgens / Q000494:pharmacology; D001681:Biological Assay; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008156:Luciferases / Q000032:analysis; D048369:MAP Kinase Kinase 1; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics* / Q000494:pharmacology*; D010957:Plasmids; D017430:Prostate-Specific Antigen / Q000096:biosynthesis* / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000494:pharmacology*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000728:Androgens; D017931:DNA Primers; D008156:Luciferases; D017346:Protein Serine-Threonine Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; D017430:Prostate-Specific Antigen