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Endogenous Bone Morphogenetic Protein-7 Controls the Motility of Prostate Cancer Cells Through Regulation of Bone Morphogenetic Protein Antagonists.
- Source :
- Journal of Urology; Sep2007, Vol. 178 Issue 3, p1086-1091, 6p
- Publication Year :
- 2007
-
Abstract
- 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<superscript> ΔBMP7</superscript>) or with an empty plasmid (PC-3<superscript>pcDNA/GFP</superscript>) 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<superscript> ΔBMP7</superscript> was 231.3 ± 28.6 vs 7.1 ± 4.4 for the WT cell line PC-3<superscript>WT</superscript> and 2.7 ± 2 for PC-3<superscript>pcDNA/GFP</superscript> (each p <0.001). BMP-7 knockdown in PC-3 cells significantly increased motility with a migrating cell number for PC-3<superscript> ΔBMP7</superscript> of 24 ± 7.5 compared with 10.2 ± 4.5 for PC-3<superscript>WT</superscript> and 11.3 ± 7.5 for PC-3<superscript>pcDNA/GFP</superscript> (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<superscript>FAK</superscript>). 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. [Copyright &y& Elsevier]
- Subjects :
- PROSTATE cancer
GROWTH factors
MALE reproductive organs
CANCER cells
Subjects
Details
- Language :
- English
- ISSN :
- 00225347
- Volume :
- 178
- Issue :
- 3
- Database :
- Supplemental Index
- Journal :
- Journal of Urology
- Publication Type :
- Academic Journal
- Accession number :
- 26152615
- Full Text :
- https://doi.org/10.1016/j.juro.2007.05.003