Source:http://linkedlifedata.com/resource/pubmed/id/18607066
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2008-7-8
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| pubmed:abstractText |
Mitochondrial dysfunction resulting from mitochondrial DNA (mtDNA) mutations and/or depletion has been correlated with cancer progression and drug resistance. To investigate the role of mtDNA in prostate cancer progression, we used LNCaP and PC-3 prostate carcinoma cells as experimental model. Compared to minimally invasive androgen-dependent LNCaP cells, highly invasive androgen-independent PC-3 cells, as well as androgen-independent DU145 and C4-2 cells, exhibited significantly reduced mtDNA content. In PC-3 cells, reduction of mtDNA was accompanied by decreased mitochondrial membrane potential (DeltaPsi(m)), increased migration onto the basement membrane protein laminin-1, reduced chemosensitivity to paclitaxel (IC(50)=110 nM vs. 22 nM) and decreased expression of poly(ADP-ribose) polymerase (PARP)-1. To investigate the relationship between mtDNA depletion and these phenotypic characteristics, we established mtDNA-depleted LNCaP cells [Rho(-)] by long-term exposure to ethidium bromide or treated wild-type LNCaP cells with a mitochondrial ionophore, carbonyl cyanide m-chlorophenylhydrazone. Both manipulations resulted in DeltaPsi(m) loss, acquisition of invasive cytology, increased motility onto laminin-1, reduced sensitivity to paclitaxel (IC(50)= approximately 100 nM) and approximately 75% reduction in PARP-1 protein levels, resembling PC-3 cells. Overall, these results provide novel evidence demonstrating that mtDNA depletion in early prostate carcinoma may contribute to the acquisition of a more invasive phenotype that is less sensitive to paclitaxel-induced apoptosis.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Androgens,
http://linkedlifedata.com/resource/pubmed/chemical/Carcinogens,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Mitochondrial,
http://linkedlifedata.com/resource/pubmed/chemical/Ethidium,
http://linkedlifedata.com/resource/pubmed/chemical/PARP1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Paclitaxel,
http://linkedlifedata.com/resource/pubmed/chemical/Poly(ADP-ribose) Polymerases
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| pubmed:status |
MEDLINE
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| pubmed:issn |
1570-5870
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
30
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
307-22
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| pubmed:meshHeading |
pubmed-meshheading:18607066-Androgens,
pubmed-meshheading:18607066-Apoptosis,
pubmed-meshheading:18607066-Carcinogens,
pubmed-meshheading:18607066-Cell Line, Tumor,
pubmed-meshheading:18607066-Cell Migration Assays,
pubmed-meshheading:18607066-Cell Movement,
pubmed-meshheading:18607066-Cell Transformation, Neoplastic,
pubmed-meshheading:18607066-DNA, Mitochondrial,
pubmed-meshheading:18607066-Drug Resistance, Neoplasm,
pubmed-meshheading:18607066-Ethidium,
pubmed-meshheading:18607066-Humans,
pubmed-meshheading:18607066-Male,
pubmed-meshheading:18607066-Membrane Potential, Mitochondrial,
pubmed-meshheading:18607066-Neoplasm Invasiveness,
pubmed-meshheading:18607066-Neoplasms, Hormone-Dependent,
pubmed-meshheading:18607066-Paclitaxel,
pubmed-meshheading:18607066-Poly(ADP-ribose) Polymerases,
pubmed-meshheading:18607066-Prostatic Neoplasms
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| pubmed:year |
2008
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| pubmed:articleTitle |
Mitochondrial DNA depletion reduces PARP-1 levels and promotes progression of the neoplastic phenotype in prostate carcinoma.
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| pubmed:affiliation |
Institute of Biomembranes and Bioenergetics, National Research Council (CNR), Bari 70126, Italy. l.moro@ibbe.cnr.it
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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