pubmed-article:21471222 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:21471222 | lifeskim:mentions | umls-concept:C0006142 | lld:lifeskim |
pubmed-article:21471222 | lifeskim:mentions | umls-concept:C0087111 | lld:lifeskim |
pubmed-article:21471222 | lifeskim:mentions | umls-concept:C0041904 | lld:lifeskim |
pubmed-article:21471222 | lifeskim:mentions | umls-concept:C0728747 | lld:lifeskim |
pubmed-article:21471222 | lifeskim:mentions | umls-concept:C0162493 | lld:lifeskim |
pubmed-article:21471222 | lifeskim:mentions | umls-concept:C0683598 | lld:lifeskim |
pubmed-article:21471222 | lifeskim:mentions | umls-concept:C0086597 | lld:lifeskim |
pubmed-article:21471222 | pubmed:issue | 21 | lld:pubmed |
pubmed-article:21471222 | pubmed:dateCreated | 2011-5-23 | lld:pubmed |
pubmed-article:21471222 | pubmed:abstractText | Trastuzumab resistance emerges to be a major issue in anti-human epidermal growth factor receptor 2 (HER2) therapy for breast cancers. Here, we demonstrated that miR-21 expression was up-regulated and its function was elevated in HER2(+) BT474, SKBR3, and MDA-MB-453 breast cancer cells that are induced to acquire trastuzumab resistance by long-term exposure to the antibody, whereas protein expression of the PTEN gene, a miR-21 target, was reduced. Blocking the action of miR-21 with antisense oligonucleotides re-sensitized the resistant cells to the therapeutic activities of trastuzumab by inducing growth arrest, proliferation inhibition, and G(1)-S cell cycle checking in the presence of the antibody. Ectopic expression of miR-21 in HER2(+) breast cancer cells confers resistance to trastuzumab. Rescuing PTEN expression with a p3XFLAG-PTEN-mut construct with deleted miR-21 targeting sequence at its 3' UTR restored the growth inhibition of trastuzumab in the resistant cells by inducing PTEN activation and AKT inhibition. In vivo, administering miR-21 antisense oligonucleotides restored trastuzumab sensitivity in the resistant breast cancer xenografts by inducing PTEN expression, whereas injection of miR-21 mimics conferred trastuzumab resistant in the sensitive breast tumors via PTEN silence. Up-regulatin of miR-21 in tumor biopsies obtained from patients receiving pre-operative trastuzumab therapy was associated with poor trastuzumab response. Therefore, miR-21 overexpression contributes to trastuzumab resistance in HER2(+) breast cancers and antagonizing miR-21 demonstrates therapeutic potential by sensitizing the malignancy to anti-HER2 treatment. | lld:pubmed |
pubmed-article:21471222 | pubmed:language | eng | lld:pubmed |
pubmed-article:21471222 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:21471222 | pubmed:citationSubset | IM | lld:pubmed |
pubmed-article:21471222 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:21471222 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:21471222 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:21471222 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:21471222 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:21471222 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:21471222 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:21471222 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:21471222 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:21471222 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:21471222 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:21471222 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:21471222 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:21471222 | pubmed:month | May | lld:pubmed |
pubmed-article:21471222 | pubmed:issn | 1083-351X | lld:pubmed |
pubmed-article:21471222 | pubmed:author | pubmed-author:BoydR LRL | lld:pubmed |
pubmed-article:21471222 | pubmed:author | pubmed-author:WangYingY | lld:pubmed |
pubmed-article:21471222 | pubmed:author | pubmed-author:SongErweiE | lld:pubmed |
pubmed-article:21471222 | pubmed:author | pubmed-author:WuWeiW | lld:pubmed |
pubmed-article:21471222 | pubmed:author | pubmed-author:SuFengxiF | lld:pubmed |
pubmed-article:21471222 | pubmed:author | pubmed-author:GongChangC | lld:pubmed |
pubmed-article:21471222 | pubmed:author | pubmed-author:YaoHeruiH | lld:pubmed |
pubmed-article:21471222 | pubmed:author | pubmed-author:ChenJianingJ | lld:pubmed |
pubmed-article:21471222 | pubmed:author | pubmed-author:YaoYandanY | lld:pubmed |
pubmed-article:21471222 | pubmed:issnType | Electronic | lld:pubmed |
pubmed-article:21471222 | pubmed:day | 27 | lld:pubmed |
pubmed-article:21471222 | pubmed:volume | 286 | lld:pubmed |
pubmed-article:21471222 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:21471222 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:21471222 | pubmed:pagination | 19127-37 | lld:pubmed |
pubmed-article:21471222 | pubmed:dateRevised | 2011-11-17 | lld:pubmed |
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pubmed-article:21471222 | pubmed:meshHeading | pubmed-meshheading:21471222... | lld:pubmed |
pubmed-article:21471222 | pubmed:year | 2011 | lld:pubmed |
pubmed-article:21471222 | pubmed:articleTitle | Up-regulation of miR-21 mediates resistance to trastuzumab therapy for breast cancer. | lld:pubmed |
pubmed-article:21471222 | pubmed:affiliation | Breast Tumor Center, Sun-Yat-Sen Memorial Hospital, Sun-Yat-Sen University, Guangzhou 510120, China. | lld:pubmed |
pubmed-article:21471222 | pubmed:publicationType | Journal Article | lld:pubmed |
pubmed-article:21471222 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
entrez-gene:406991 | entrezgene:pubmed | pubmed-article:21471222 | lld:entrezgene |
http://linkedlifedata.com/r... | entrezgene:pubmed | pubmed-article:21471222 | lld:entrezgene |