rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2009-2-4
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pubmed:abstractText |
High levels of the cyclooxygenase-2 (COX-2) protein have been associated with invasion and metastasis of breast tumors. Both prostaglandin E(2) (PGE(2)) and interleukin-8 (IL-8) have been shown to mediate the invasive activity of COX-2 in breast cancer cells. Here we expand these studies to determine how COX-2 uses PGE(2) and IL-8 to induce breast cancer cell invasion. We demonstrated that PGE(2) and IL-8 decreased the expression of the tumor suppressor protein Programmed Cell Death 4 (PDCD4). We hypothesized that suppression of PDCD4 expression is vital to the invasive activity of PGE(2) and IL-8. In MCF-7 cells overexpressing PDCD4 (MCF-7/PDCD4), PGE(2) and IL-8 failed to induce invasion, in contrast to the parental MCF-7 cells, thus indicating that PDCD4 blocks breast cancer cell invasion. MCF-7/PDCD4 cells produced higher levels of the Tissue Inhibitor of Metalloproteinases-2 (TIMP-2) than the parental cells. Silencing TIMP-2 mRNA in MCF-7/PDCD4 cells reversed the anti-invasive effects of PDCD4, allowing PGE(2) and IL-8 to induce the invasion of these cells. Here we report the novel findings that suppression of PDCD4 expression is vital for the invasive activity of COX-2 mediated by PGE(2) and IL-8, and that PDCD4 increases TIMP-2 expression to inhibit breast cancer cell invasion.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18386173-10570194,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18386173-11135226,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18386173-11314000,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18386173-11402303,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18386173-11494140,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18386173-11830510,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/18386173-12784332,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/18386173-16274040,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/18386173-9815852
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-8,
http://linkedlifedata.com/resource/pubmed/chemical/PDCD4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PTGS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/RNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tissue Inhibitor of...
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1573-7217
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pubmed:author |
|
pubmed:issnType |
Electronic
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pubmed:volume |
114
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
203-9
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:18386173-Apoptosis Regulatory Proteins,
pubmed-meshheading:18386173-Blotting, Western,
pubmed-meshheading:18386173-Breast Neoplasms,
pubmed-meshheading:18386173-Cyclooxygenase 2,
pubmed-meshheading:18386173-Dinoprostone,
pubmed-meshheading:18386173-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:18386173-Female,
pubmed-meshheading:18386173-Gene Expression,
pubmed-meshheading:18386173-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:18386173-Humans,
pubmed-meshheading:18386173-Interleukin-8,
pubmed-meshheading:18386173-Neoplasm Invasiveness,
pubmed-meshheading:18386173-RNA, Messenger,
pubmed-meshheading:18386173-RNA, Small Interfering,
pubmed-meshheading:18386173-RNA Interference,
pubmed-meshheading:18386173-RNA-Binding Proteins,
pubmed-meshheading:18386173-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:18386173-Tissue Inhibitor of Metalloproteinase-2,
pubmed-meshheading:18386173-Tumor Cells, Cultured
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pubmed:year |
2009
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pubmed:articleTitle |
Programmed cell death 4 inhibits breast cancer cell invasion by increasing tissue inhibitor of metalloproteinases-2 expression.
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pubmed:affiliation |
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Unit 422, Houston, TX 77030, 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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