Platelet-derived growth factor-D contributes to aggressiveness of breast cancer cells by up-regulating Notch and NF-jB signaling pathways
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Aamir Ahmad Zhiwei Wang Dejuan Kong Raza Ali Shadan Ali Sanjeev Banerjee Fazlul H. Sarkar
- چاپ و سال / کشور: 2010
Description
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 MDAMB- 231 and SUM-149 are more invasive compared to cell lines with little or no expression of PDGF-D such as MDAMB- 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-jB 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-jB and our findings are consistent showing that PDGF-D over-expression led to increased DNA binding activity of NF-jB 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-jB 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-jB signaling.
Breast Cancer Res Treat (2011) 126:15–25 Received: 4 March 2010 / Accepted: 31 March 2010 / Published online: 9 April 2010 Springer Science+Business Media, LLC. 2010
