| Platelet-derived growth factor-D contributes to aggressiveness of breast cancer cells by up-regulating Notch and NF-κB signaling pathways. | |
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MedLine Citation:
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PMID: 20379844 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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. |
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Authors:
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Aamir Ahmad; Zhiwei Wang; Dejuan Kong; Raza Ali; Shadan Ali; Sanjeev Banerjee; Fazlul H Sarkar |
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Publication Detail:
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Type: Journal Article Date: 2010-04-09 |
Journal Detail:
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Title: Breast cancer research and treatment Volume: 126 ISSN: 1573-7217 ISO Abbreviation: Breast Cancer Res. Treat. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-24 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8111104 Medline TA: Breast Cancer Res Treat Country: Netherlands |
Other Details:
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Languages: eng Pagination: 15-25 Citation Subset: IM |
Affiliation:
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Department of Pathology, Barbara Ann Karmanos Cancer Center, Wayne State University School of Medicine, 740 HWCRC Bldg, 4100 John R Street, Detroit, MI, 48201, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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