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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
33
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pubmed:dateCreated |
2007-7-19
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pubmed:abstractText |
Acquisition of drug resistance is one of the main obstacles encountered in cancer chemotherapy. Overexpression of multi-drug resistance 1 (MDR1) gene and its protein product P-glycoprotein, accompanied with a decrease in doxorubicin accumulation level, was observed in doxorubicin-resistant R-HepG2 cells, a subline derived by selection of human hepatocellular carcinoma HepG2 cells with doxorubicin. In addition, Northern-blot analysis revealed an eight fold upregulation of the imprinted H19 mRNA in R-HepG2 cells. H19 knockdown by transfection with antisense H19 oligonucleotides suppressed the MDR1/P-glycoprotein expression, increased the cellular doxorubicin accumulation level and sensitized doxorubicin toxicity in both HepG2 parent cells and R-HepG2 cells. Results from methylation-specific polymerase chain reaction analysis indicated that the MDR1 gene promoter was hypomethylated in R-HepG2 cells. Antisense H19 oligonucleotides transfection induced a marked increase in the percentage of MDR1 promoter methylation and decrease in MDR1 expression in R-HepG2 cells. Thus, the H19 gene is believed to induce P-glycoprotein expression and MDR1-associated drug resistance at least in liver cancer cells through regulation of MDR1 promoter methylation.
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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/Antibiotics, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/Doxorubicin,
http://linkedlifedata.com/resource/pubmed/chemical/H19 long non-coding RNA,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/P-Glycoprotein,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Untranslated
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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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 |
19
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pubmed:volume |
26
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4877-81
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pubmed:dateRevised |
2011-10-7
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pubmed:meshHeading |
pubmed-meshheading:17297456-Antibiotics, Antineoplastic,
pubmed-meshheading:17297456-Blotting, Northern,
pubmed-meshheading:17297456-Blotting, Western,
pubmed-meshheading:17297456-Carcinoma, Hepatocellular,
pubmed-meshheading:17297456-Cell Line, Tumor,
pubmed-meshheading:17297456-Cell Survival,
pubmed-meshheading:17297456-DNA Methylation,
pubmed-meshheading:17297456-Dose-Response Relationship, Drug,
pubmed-meshheading:17297456-Doxorubicin,
pubmed-meshheading:17297456-Drug Resistance, Neoplasm,
pubmed-meshheading:17297456-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:17297456-Humans,
pubmed-meshheading:17297456-Liver Neoplasms,
pubmed-meshheading:17297456-Oligonucleotides, Antisense,
pubmed-meshheading:17297456-P-Glycoprotein,
pubmed-meshheading:17297456-Promoter Regions, Genetic,
pubmed-meshheading:17297456-RNA, Messenger,
pubmed-meshheading:17297456-RNA, Small Interfering,
pubmed-meshheading:17297456-RNA, Untranslated,
pubmed-meshheading:17297456-Transfection
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pubmed:year |
2007
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pubmed:articleTitle |
Riboregulator H19 induction of MDR1-associated drug resistance in human hepatocellular carcinoma cells.
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pubmed:affiliation |
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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