| pubmed-article:17662692 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:17662692 | lifeskim:mentions | umls-concept:C1517806 | lld:lifeskim |
| pubmed-article:17662692 | lifeskim:mentions | umls-concept:C2266856 | lld:lifeskim |
| pubmed-article:17662692 | pubmed:issue | 2 | lld:pubmed |
| pubmed-article:17662692 | pubmed:dateCreated | 2007-8-7 | lld:pubmed |
| pubmed-article:17662692 | pubmed:abstractText | Overexpression of MDR-1 represents a critical mechanism of drug resistance in cancer. Proteasome inhibitors recently entered the clinic for treatment of multiple myeloma. We provide evidence that the proteasome-inhibitors Bortezomib and MLN273 are both substrates of MDR-1 by using knockdown of MDR-1 via a transposon-based vector system stably expressing siRNA against MDR-1 in MDR-1-overexpressing K562/Dox cells. Notably, the efficacy of MLN273 (EC(50) from 253 ng/ml in MDR-1(+) to 9.7 ng/ml in MDR-1(-) cells) was much more dependent on MDR-1 expression than Bortezomib (EC(50) from 24.9 ng/ml in MDR-1(+) to 4.5 ng/ml in MDR-1(-) cells). Growth inhibition in MDR-1 negative cells was in part due to increased rate of apoptosis. The enhanced inhibitory effect on the proteasome by loss of MDR-1 was corroborated by a reduced proteasomal activity. Our report provides evidence that MLN273 and, to a lesser degree, Bortezomib are both MDR-1-substrates, which might be relevant for drug-resistance in cancer. | lld:pubmed |
| pubmed-article:17662692 | pubmed:language | eng | lld:pubmed |
| pubmed-article:17662692 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17662692 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:17662692 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17662692 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17662692 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17662692 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17662692 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17662692 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:17662692 | pubmed:month | Sep | lld:pubmed |
| pubmed-article:17662692 | pubmed:issn | 0006-291X | lld:pubmed |
| pubmed-article:17662692 | pubmed:author | pubmed-author:GastlGuenther... | lld:pubmed |
| pubmed-article:17662692 | pubmed:author | pubmed-author:TilgHerbertH | lld:pubmed |
| pubmed-article:17662692 | pubmed:author | pubmed-author:RumpoldHolger... | lld:pubmed |
| pubmed-article:17662692 | pubmed:author | pubmed-author:WolfAnna... | lld:pubmed |
| pubmed-article:17662692 | pubmed:author | pubmed-author:WolfDominikD | lld:pubmed |
| pubmed-article:17662692 | pubmed:author | pubmed-author:SalvadorChris... | lld:pubmed |
| pubmed-article:17662692 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:17662692 | pubmed:day | 21 | lld:pubmed |
| pubmed-article:17662692 | pubmed:volume | 361 | lld:pubmed |
| pubmed-article:17662692 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:17662692 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:17662692 | pubmed:pagination | 549-54 | lld:pubmed |
| pubmed-article:17662692 | pubmed:meshHeading | pubmed-meshheading:17662692... | lld:pubmed |
| pubmed-article:17662692 | pubmed:meshHeading | pubmed-meshheading:17662692... | lld:pubmed |
| pubmed-article:17662692 | pubmed:meshHeading | pubmed-meshheading:17662692... | lld:pubmed |
| pubmed-article:17662692 | pubmed:meshHeading | pubmed-meshheading:17662692... | lld:pubmed |
| pubmed-article:17662692 | pubmed:meshHeading | pubmed-meshheading:17662692... | lld:pubmed |
| pubmed-article:17662692 | pubmed:meshHeading | pubmed-meshheading:17662692... | lld:pubmed |
| pubmed-article:17662692 | pubmed:meshHeading | pubmed-meshheading:17662692... | lld:pubmed |
| pubmed-article:17662692 | pubmed:meshHeading | pubmed-meshheading:17662692... | lld:pubmed |
| pubmed-article:17662692 | pubmed:meshHeading | pubmed-meshheading:17662692... | lld:pubmed |
| pubmed-article:17662692 | pubmed:meshHeading | pubmed-meshheading:17662692... | lld:pubmed |
| pubmed-article:17662692 | pubmed:year | 2007 | lld:pubmed |
| pubmed-article:17662692 | pubmed:articleTitle | Knockdown of PgP resensitizes leukemic cells to proteasome inhibitors. | lld:pubmed |
| pubmed-article:17662692 | pubmed:affiliation | Laboratory of Molecular Genetics, Department of Hematology and Oncology, Medical University Innsbruck, Innsbruck, Austria. | lld:pubmed |
| pubmed-article:17662692 | pubmed:publicationType | Journal Article | lld:pubmed |
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