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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
177
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pubmed:dateCreated |
2011-6-15
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pubmed:databankReference |
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pubmed:abstractText |
The basal-like subtype of breast cancer has an aggressive clinical behavior compared to that of the luminal subtype. We identified the microRNAs (miRNAs) miR-221 and miR-222 (miR-221/222) as basal-like subtype-specific miRNAs and showed that expression of miR-221/222 decreased expression of epithelial-specific genes and increased expression of mesenchymal-specific genes, and increased cell migration and invasion in a manner characteristic of the epithelial-to-mesenchymal transition (EMT). The transcription factor FOSL1 (also known as Fra-1), which is found in basal-like breast cancers but not in the luminal subtype, stimulated the transcription of miR-221/222, and the abundance of these miRNAs decreased with inhibition of the epidermal growth factor receptor (EGFR) or MEK (mitogen-activated or extracellular signal-regulated protein kinase kinase), placing miR-221/222 downstream of the RAS pathway. Furthermore, miR-221/222-mediated reduction in E-cadherin abundance depended on their targeting the 3' untranslated region of the GATA family transcriptional repressor TRPS1 (tricho-rhino-phalangeal syndrome type 1), which inhibited EMT by decreasing ZEB2 (zinc finger E-box-binding homeobox2) expression. We conclude that by promoting EMT, miR-221/222 may contribute to the more aggressive clinical behavior of basal-like breast cancers.
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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/3' Untranslated Regions,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/EGFR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/MIRN221 microRNA, human,
http://linkedlifedata.com/resource/pubmed/chemical/MIRN222 microRNA, human,
http://linkedlifedata.com/resource/pubmed/chemical/MicroRNAs,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fos,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TRPS1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/ZEB2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/fos-related antigen 1,
http://linkedlifedata.com/resource/pubmed/chemical/ras Proteins
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pubmed:status |
MEDLINE
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pubmed:issn |
1937-9145
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pubmed:author |
pubmed-author:AdaiAlex TAT,
pubmed-author:AmlerLukasL,
pubmed-author:BourgonRichardR,
pubmed-author:BoydZacharyZ,
pubmed-author:DornanDavidD,
pubmed-author:JanuarioThomasT,
pubmed-author:JhunjhunwalaSuchitS,
pubmed-author:KimHyo-JinHJ,
pubmed-author:LacknerMark RMR,
pubmed-author:ModrusanZoraZ,
pubmed-author:MrozWW,
pubmed-author:NewmanRobert JRJ,
pubmed-author:O'BrienCarolC,
pubmed-author:SpoerkeJillJ,
pubmed-author:SternHoward MHM,
pubmed-author:StinsonSusannaS,
pubmed-author:WarmingSørenS,
pubmed-author:YehRu-FangRF,
pubmed-author:YuNancyN,
pubmed-author:de SauvageFrederic JFJ
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pubmed:issnType |
Electronic
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pubmed:volume |
4
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
ra41
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pubmed:meshHeading |
pubmed-meshheading:21673316-3' Untranslated Regions,
pubmed-meshheading:21673316-Breast Neoplasms,
pubmed-meshheading:21673316-Cell Line, Tumor,
pubmed-meshheading:21673316-DNA-Binding Proteins,
pubmed-meshheading:21673316-Epithelial-Mesenchymal Transition,
pubmed-meshheading:21673316-Female,
pubmed-meshheading:21673316-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:21673316-Homeodomain Proteins,
pubmed-meshheading:21673316-Humans,
pubmed-meshheading:21673316-MAP Kinase Kinase Kinases,
pubmed-meshheading:21673316-MicroRNAs,
pubmed-meshheading:21673316-Proto-Oncogene Proteins c-fos,
pubmed-meshheading:21673316-RNA, Neoplasm,
pubmed-meshheading:21673316-Receptor, Epidermal Growth Factor,
pubmed-meshheading:21673316-Repressor Proteins,
pubmed-meshheading:21673316-Transcription Factors,
pubmed-meshheading:21673316-ras Proteins
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pubmed:year |
2011
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pubmed:articleTitle |
TRPS1 targeting by miR-221/222 promotes the epithelial-to-mesenchymal transition in breast cancer.
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pubmed:affiliation |
Department of Molecular Diagnostics and Cancer Cell Biology, Genentech Inc., South San Francisco, CA 94080, USA.
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pubmed:publicationType |
Journal Article
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