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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
2011-7-22
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pubmed:abstractText |
Drug resistance remains a clinical challenge in cancer treatment due to poor understanding of underlying mechanisms. We have established several drug-resistant prostate cancer cell lines by long-term culture in medium containing chemotherapeutic drugs. These resistant lines displayed a significant increase in side population cells due to overexpression of drug efflux pumps including ABCG2/BCRP and MDR1/Pgp. To uncover potential mechanisms underlying drug resistance, we performed microarray analysis to identify differentially expressed genes in 2 drug-resistant lines. We observed that POU5F1/OCT4, a transcription factor key to regulating pluripotency in embryonic stem cells, was upregulated in drug-resistant lines and accompanied by transcriptional activation of a set of its known target genes. Upregulation of OCT4 in drug-resistant cells was validated by RT-PCR and sequencing of PCR products as well as confirmation by Western blot and specific shRNA knockdown. Analysis of the regulatory region of POU5F1/OCT4 revealed a reduction of methylation in drug-resistant cell lines. Furthermore, these drug-resistant cells exhibited a significant increase in tumorigenicity in vivo. Subcutaneous inoculation of as few as 10 drug-resistant cells could initiate tumor formation in SCID mice, whereas no detectable tumors were observed from the parental line under similar conditions, suggesting that these drug-resistant cells may be enriched for tumor-initiating cells. Knocking down OCT4 expression by specific shRNAs attenuated growth of drug-resistant cells. Our data suggest that OCT4 re-expression in cancer cells may play an important role in carcinogenesis and provide one possible mechanism by which cancer cells acquire/maintain a drug-resistant phenotype.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-11781821,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-11900250,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-14576842,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-14981536,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-15120036,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-15256465,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-15381773,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-15470214,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-15738542,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-15882627,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-16024622,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-16153702,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-16765145,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-16951404,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-17045208,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-17314394,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-17379765,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-17425502,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-17548060,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-17761754,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-18032701,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-18056989,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-18371374,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-18487012,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-18594202,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-18627312,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-18949397,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-19047143,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-19058139,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-19221599,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-19244107,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-19345326,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-19483170,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-19733480,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-20027182,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-20145614,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-20579941,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-2880583,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21779471-8666936
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pubmed:language |
eng
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pubmed:journal |
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pubmed:status |
PubMed-not-MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1947-6027
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
1
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
908-16
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pubmed:year |
2010
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pubmed:articleTitle |
A Role for OCT4 in Tumor Initiation of Drug-Resistant Prostate Cancer Cells.
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pubmed:affiliation |
Department of Pharmacology & Experimental Therapeutics and The Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
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pubmed:publicationType |
Journal Article
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