Source:http://linkedlifedata.com/resource/pubmed/id/16997127
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1-2
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pubmed:dateCreated |
2006-9-25
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pubmed:abstractText |
The lipid-peroxidating enzyme, 15-lipoxygenase (LO)-1 and its metabolite, 13-S-hydroxyoctadecadienoic acid (13-S-HODE), likely contribute to prostate tumorigenesis. Thus, this study evaluated adenovirus-mediated overexpression of 15-LO-1 on normal mouse prostate. Adenovirus expressing either human 15-LO-1 tagged with green fluorescent protein (GFP) or GFP alone was orthotopically injected into the dorsolateral prostates of C57BL/6 mice, three times over the course of 60 days. On day 90, pathological changes in prostate tissue were assessed by hematoxylin and eosin (H&E) staining. Expression of the proliferation marker Ki-67 was evaluated by immunohistochemistry and expression of angiogenesis markers were analyzed by an antibody array. Based on the latter study, immunoprecipitation analysis was used to measure the effect of 13-S-HODE, with or without conditioned media, on fibroblast growth factor-a and b (FGF-a and FGF-b) expression in human PrEC (normal prostate epithelial), PrSMC (normal prostate smooth muscle) and PrSC (normal prostate stromal) lines. Expression of viral 15-LO-1-GFP, but not GFP alone, resulted in the development of a prostate intraepithelial neoplasia (PIN)-like phenotype with increased expression of Ki-67. Aberrant 15-LO-1 expression also induced the angiogenic markers FGF-a and FGF-b. Human PrEC, PrSMC and PrSC lines demonstrated an increase in FGF-b expression upon stimulation with 13-S-HODE, which was further increased by the addition of conditioned media from the epithelial or smooth muscle cells. Using adenoviral mediated 15-LO-1 gene delivery, this study suggests that aberrant 15-LO-1 overexpression in normal prostate can trigger events leading to prostate epithelial and stromal cell proliferation. Thus, our findings demonstrate the effectiveness of this viral system for 15-LO-1 expression studies in tissues.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonate 15-Lipoxygenase,
http://linkedlifedata.com/resource/pubmed/chemical/Biological Markers,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Ki-67 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Mki67 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1098-8823
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
81
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1-13
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pubmed:dateRevised |
2007-12-3
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pubmed:meshHeading |
pubmed-meshheading:16997127-Adenoviridae,
pubmed-meshheading:16997127-Animals,
pubmed-meshheading:16997127-Arachidonate 15-Lipoxygenase,
pubmed-meshheading:16997127-Biological Markers,
pubmed-meshheading:16997127-Cell Line,
pubmed-meshheading:16997127-Humans,
pubmed-meshheading:16997127-Isoenzymes,
pubmed-meshheading:16997127-Ki-67 Antigen,
pubmed-meshheading:16997127-Male,
pubmed-meshheading:16997127-Mice,
pubmed-meshheading:16997127-Mice, Inbred C57BL,
pubmed-meshheading:16997127-Neovascularization, Pathologic,
pubmed-meshheading:16997127-Prostate,
pubmed-meshheading:16997127-Prostatic Neoplasms,
pubmed-meshheading:16997127-Recombinant Fusion Proteins
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pubmed:year |
2006
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pubmed:articleTitle |
Orthotopic expression of human 15-lipoxygenase (LO)-1 in the dorsolateral prostate of normal wild-type C57BL/6 mouse causes PIN-like lesions.
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pubmed:affiliation |
Department of Urology, University of Pittsburgh and Cancer Institute, PA 15232, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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