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Molecular and Cellular Biochemistry

, Volume 349, Issue 1–2, pp 33–40 | Cite as

Growth and differentiation factor 9 (GDF-9) induces epithelial–mesenchymal transition in prostate cancer cells

  • Sivan M. Bokobza
  • Lin Ye
  • Howard Kynaston
  • Wen G. JiangEmail author
Article

Abstract

The role of bone morphogenetic proteins in the progression and metastasis of prostate cancer is a topic that has undergone extensive research. This study investigates the role of BMP member growth and differentiation factor 9 (GDF-9) in the progression of this disease. GDF-9 was over-expressed and knocked-down in PC-3 cells, respectively. Furthermore, along with the use of a generated recombinant GDF-9 protein, these cells were then analyzed for any changes in their invasiveness and expression of epithelial–mesenchymal transition (EMT) associated genes. GDF-9 was shown to promote the invasiveness of PC-3 cells together with an induction in the expression of genes including SNAI1, RhoC, ROCK-1, and N-cadherin, while reducing levels of E-cadherin. These expression changes are characteristic of the onset of EMT, and resulted in the cells having a more mesenchymal-like morphology. Treating these cells with activin-like kinase-5 (ALK-5) inhibitor, demonstrated that GDF-9 induced up-regulation of these molecules was ALK-5 dependant. This study shows that in PC-3 cells, GDF-9 signaling via ALK-5, can promote cell invasiveness via a complex network of signaling molecules that work together to trigger the process of EMT, and thereby aid in the aggressiveness and progression of prostate cancer cells.

Keywords

Bone morphogenetic protein GDF-9 Prostate cancer SNAI1 EMT 

Notes

Acknowledgment

This work was supported by the Dezna Robins Jones Charitable foundation and Cancer Research Wales.

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Sivan M. Bokobza
    • 1
  • Lin Ye
    • 1
  • Howard Kynaston
    • 1
  • Wen G. Jiang
    • 1
    Email author
  1. 1.Metastasis and Angiogenesis Research Group, Department of SurgeryCardiff University School of MedicineCardiffUK

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