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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
24
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pubmed:dateCreated |
2010-12-16
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pubmed:abstractText |
The role of mammary epithelial cell (MEC) NF-?B in tumor progression in vivo is unknown, as murine NF-?B components and kinases either are required for murine survival or interfere with normal mammary gland development. As NF-?B inhibitors block both tumor-associated macrophages (TAM) and MEC NF-?B, the importance of MEC NF-?B to tumor progression in vivo remained to be determined. Herein, an MEC-targeted inducible transgenic inhibitor of NF-?B (I?B?SR) was developed in ErbB2 mammary oncomice. Inducible suppression of NF-?B in the adult mammary epithelium delayed the onset and number of new tumors. Within similar sized breast tumors, TAM and tumor neoangiogenesis was reduced. Coculture experiments demonstrated MEC NF-?B enhanced TAM recruitment. Genome-wide expression and proteomic analysis showed that I?B?SR inhibited tumor stem cell pathways. I?B?SR inhibited breast tumor stem cell markers in transgenic tumors, reduced stem cell expansion in vitro, and repressed expression of Nanog and Sox2 in vivo and in vitro. MEC NF-?B contributes to mammary tumorigenesis. As we show that NF-?B contributes to expansion of breast tumor stem cells and heterotypic signals that enhance TAM and vasculogenesis, these processes may contribute to NF-?B-dependent mammary tumorigenesis.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1538-7445
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pubmed:author |
pubmed-author:AlbaneseChristopherC,
pubmed-author:CasimiroMathew CMC,
pubmed-author:JiaoXuanmaoX,
pubmed-author:JoyceDavidD,
pubmed-author:JuXiaomingX,
pubmed-author:KatiyarSanjayS,
pubmed-author:LisantiMichael PMP,
pubmed-author:LiuManranM,
pubmed-author:OjeifoJohnJ,
pubmed-author:PestellRichard GRG,
pubmed-author:QuongAndrew AAA,
pubmed-author:SakamakiToshiyukiT,
pubmed-author:ShirleyL AndrewLA,
pubmed-author:WillmarthNicole ENE,
pubmed-author:YeowWen-ShuzWS
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pubmed:copyrightInfo |
©2010 AACR.
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
70
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10464-73
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pubmed:dateRevised |
2011-10-6
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pubmed:meshHeading |
pubmed-meshheading:21159656-Animals,
pubmed-meshheading:21159656-Cell Growth Processes,
pubmed-meshheading:21159656-Cell Transformation, Neoplastic,
pubmed-meshheading:21159656-Epithelial Cells,
pubmed-meshheading:21159656-Epithelial-Mesenchymal Transition,
pubmed-meshheading:21159656-Female,
pubmed-meshheading:21159656-I-kappa B Proteins,
pubmed-meshheading:21159656-Mammary Neoplasms, Experimental,
pubmed-meshheading:21159656-Mice,
pubmed-meshheading:21159656-Mice, Transgenic,
pubmed-meshheading:21159656-NF-kappa B,
pubmed-meshheading:21159656-Neoplastic Stem Cells,
pubmed-meshheading:21159656-Reactive Oxygen Species,
pubmed-meshheading:21159656-Receptor, erbB-2,
pubmed-meshheading:21159656-Transfection
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pubmed:year |
2010
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pubmed:articleTitle |
The canonical NF-kappaB pathway governs mammary tumorigenesis in transgenic mice and tumor stem cell expansion.
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pubmed:affiliation |
Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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