title: Endogenous bone morphogenetic protein-7 controls the motility of prostate cancer cells through regulation of bone morphogenetic protein antagonists.
abstract: OBJECTIVE
  We investigated the effect of manipulating endogenous BMP-7 expression on the invasion and motility of prostate cancer cells and the resulting effect on its antagonists using a ribozyme transgene.
  
  
  METHODS
  A hammerhead ribozyme transgene was synthesized and cloned into a mammalian expression vector (pcDNA3.1/nt-GFP-TOPO). PC-3 cells (American Type Culture Collection, Manassas, Virginia) were transfected with the ribozyme transgene (PC-3(DeltaBMP7)) or with an empty plasmid (PC-3(pcDNA/GFP)) by electroporation. Invasion and motility were accessed by in vitro invasion and motility assays.
  
  
  RESULTS
  The ribozyme decreased BMP-7 expression at the mRNA and protein levels in PC-3 cells. Invasive potential was significantly increased following the loss of BMP-7 expression. The mean +/- SD invading cell number for PC-3(DeltaBMP7) was 231.3 +/- 28.6 vs 7.1 +/- 4.4 for the WT cell line PC-3(WT) and 2.7 +/- 2 for PC-3(pcDNA/GFP) (each p <0.001). BMP-7 knockdown in PC-3 cells significantly increased motility with a migrating cell number for PC-3(DeltaBMP7) of 24 +/- 7.5 compared with 10.2 +/- 4.5 for PC-3(WT) and 11.3 +/- 7.5 for PC-3(pcDNA/GFP) (p <0.01 and 0.011, respectively). The change in motility was seen together with changes in the cellular location of paxillin and focal adhesion kinase (p125(FAK)). Interestingly the loss of BMP-7 resulted in decreased noggin and follistatin expression.
  
  
  CONCLUSIONS
  The loss of endogenous BMP-7 from prostate cancer cells is associated with increased invasiveness and motility, which appears to be facilitated by changes in the level of the BMP antagonists noggin and follistatin. Endogenous BMP-7 has an important role in controlling noggin and follistatin expression.
authors.affiliation: Metastasis and Angiogenesis Research Group, Department of Surgery, Cardiff University School of Medicine, Heath Park, Cardiff, United Kingdom. yel@cf.ac.uk
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Lewis-Russell
authors.forename: Howard
authors.initials: H
authors.lastname: Kynaston
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7; D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D001859:Bone Neoplasms / Q000378:metabolism / Q000556:secondary; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D038681:Follistatin / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016337:RNA, Catalytic / Q000235:genetics; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D000099176:Noggin Protein
chemical_list: D055419:Bone Morphogenetic Protein 7; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D038681:Follistatin; D016337:RNA, Catalytic; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein; C525819:BMP7 protein, human; C503233:FST protein, human; C427204:hammerhead ribozyme