Breast Cancer Research and Treatment

, Volume 126, Issue 1, pp 15–25 | Cite as

RETRACTED ARTICLE: Platelet-derived growth factor-D contributes to aggressiveness of breast cancer cells by up-regulating Notch and NF-κB signaling pathways

  • Aamir Ahmad
  • Zhiwei Wang
  • Dejuan Kong
  • Raza Ali
  • Shadan Ali
  • Sanjeev Banerjee
  • Fazlul H. Sarkar
Preclinical study

Abstract

Platelet-derived growth factor-D (PDGF-D) has been linked with several human malignancies; however, its role in breast cancer progression is not known. We found that PDGF-D expressing breast cancer cell lines MDA-MB-231 and SUM-149 are more invasive compared to cell lines with little or no expression of PDGF-D such as MDA-MB-468 and MCF-7 cells. Over-expression of PDGF-D in PDGF-D low expressing MDA-MB-468 and MCF-7 cells by cDNA transfection showed increased cell proliferation while silencing the expression of PDGF-D by siRNA in PDGF-D high expressing MDA-MB-231 and SUM-149 cells showed decreased cell proliferation and increased apoptosis. Moreover, PDGF-D over-expression was positively correlated with the expression of Notch-1 and Jagged-1, and the expression of mesenchymal markers (Vimentin and ZEB-2) with concomitant decreased expression of epithelial marker E-cadherin. Since NF-κB activation plays a crucial role in Notch signaling as well as in epithelial–mesenchymal transition and tumor aggressiveness, we determined the DNA binding activity of NF-κB and our findings are consistent showing that PDGF-D over-expression led to increased DNA binding activity of NF-κB while it was found to be decreased by inactivation of PDGF-D. These results were also consistent with the expression and activity of MMP-9 and VEGF, as well as invasive characteristics. Further, forced expression of Notch-1/Jagged-1 by cDNA transfection de-repressed the effects of PDGF-D silencing on NF-κB activity and invasion. From these results, we conclude that PDGF-D plays an important role in breast tumor aggressiveness and this process is mechanistically linked with the activation of Notch and NF-κB signaling.

Keywords

PDGF-D Breast cancer Invasion NF-κB Notch-1 Jagged-1 EMT 

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Aamir Ahmad
    • 1
  • Zhiwei Wang
    • 1
  • Dejuan Kong
    • 1
  • Raza Ali
    • 1
  • Shadan Ali
    • 2
  • Sanjeev Banerjee
    • 1
  • Fazlul H. Sarkar
    • 1
  1. 1.Department of Pathology, Barbara Ann Karmanos Cancer CenterWayne State University School of MedicineDetroitUSA
  2. 2.Department of Internal Medicine, Barbara Ann Karmanos Cancer CenterWayne State University School of MedicineDetroitUSA

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