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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
54
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pubmed:dateCreated |
2004-11-19
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pubmed:abstractText |
Unlike estrogen receptor-positive (ER(+)) breast cancers, normal human mammary epithelial cells (HMECs) typically express low nuclear levels of ER (ER poor). We previously demonstrated that 1.0 microM tamoxifen (Tam) promotes apoptosis in acutely damaged ER-poor HMECs through a rapid, 'nonclassic' signaling pathway. Interferon-regulatory factor-1 (IRF-1), a target of signal transducer and activator of transcription-1 transcriptional regulation, has been shown to promote apoptosis following DNA damage. Here we show that 1.0 microM Tam promotes apoptosis in acutely damaged ER-poor HMECs through IRF-1 induction and caspase-1/3 activation. Treatment of acutely damaged HMEC-E6 cells with 1.0 microM Tam resulted in recruitment of CBP to the gamma-IFN-activated sequence element of the IRF-1 promoter, induction of IRF-1, and sequential activation of caspase-1 and -3. The effects of Tam were blocked by expression of siRNA directed against IRF-1 and caspase-1 inhibitors. These data indicate that Tam induces apoptosis in HMEC-E6 cells through a novel IRF-1-mediated signaling pathway that results in activated caspase-1 and -3.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Hormonal,
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/IRF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factor-1,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Tamoxifen
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0950-9232
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
18
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8743-55
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:15467738-Antineoplastic Agents, Hormonal,
pubmed-meshheading:15467738-Apoptosis,
pubmed-meshheading:15467738-Base Sequence,
pubmed-meshheading:15467738-Caspase 1,
pubmed-meshheading:15467738-Caspase 3,
pubmed-meshheading:15467738-Caspases,
pubmed-meshheading:15467738-Cells, Cultured,
pubmed-meshheading:15467738-DNA Primers,
pubmed-meshheading:15467738-DNA-Binding Proteins,
pubmed-meshheading:15467738-Enzyme Induction,
pubmed-meshheading:15467738-Enzyme Inhibitors,
pubmed-meshheading:15467738-Humans,
pubmed-meshheading:15467738-Interferon Regulatory Factor-1,
pubmed-meshheading:15467738-Mammary Glands, Human,
pubmed-meshheading:15467738-Phosphoproteins,
pubmed-meshheading:15467738-Promoter Regions, Genetic,
pubmed-meshheading:15467738-RNA, Small Interfering,
pubmed-meshheading:15467738-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15467738-Tamoxifen
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pubmed:year |
2004
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pubmed:articleTitle |
Interferon-regulatory factor-1 is critical for tamoxifen-mediated apoptosis in human mammary epithelial cells.
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pubmed:affiliation |
Division of Medical Oncology, Duke University, Durham, NC 27710, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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