Endogenous bone morphogenetic protein-7 controls the motility of prostate cancer cells through regulation of bone morphogenetic protein antagonists

J Urol. 2007 Sep;178(3 Pt 1):1086-91. doi: 10.1016/j.juro.2007.05.003. Epub 2007 Jul 20.


Purpose: 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.

Materials and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Protein Receptors / metabolism
  • Bone Morphogenetic Proteins / antagonists & inhibitors*
  • Bone Morphogenetic Proteins / metabolism
  • Bone Morphogenetic Proteins / physiology
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / secondary
  • Carrier Proteins / metabolism
  • Carrier Proteins / pharmacology
  • Cell Adhesion / physiology
  • Cell Line, Tumor
  • Cell Movement*
  • Down-Regulation
  • Follistatin / metabolism
  • Follistatin / pharmacology
  • Humans
  • Male
  • Neoplasm Invasiveness / physiopathology
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / physiopathology*
  • RNA, Catalytic / genetics
  • Transfection
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / physiology*


  • BMP7 protein, human
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins
  • Carrier Proteins
  • FST protein, human
  • Follistatin
  • RNA, Catalytic
  • Transforming Growth Factor beta
  • hammerhead ribozyme
  • noggin protein
  • Bone Morphogenetic Protein Receptors