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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
18
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pubmed:dateCreated |
2002-4-29
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pubmed:databankReference |
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pubmed:abstractText |
15-Lipoxygenase 2 (15-LOX2) is a recently cloned human lipoxygenase that shows tissue-restricted expression in prostate, lung, skin, and cornea. The protein level and enzymatic activity of 15-LOX2 have been shown to be down-regulated in prostate cancers compared with normal and benign prostate tissues. The biological function of 15-LOX2 and the role of loss of 15-LOX2 expression in prostate tumorigenesis, however, remain unknown. We report the cloning and functional characterization of 15-LOX2 and its three splice variants (termed 15-LOX2sv-a, 15-LOX2sv-b, and 15-LOX2sv-c) from primary prostate epithelial cells. Western blotting with multiple primary prostate cell strains and prostate cancer cell lines reveals that the expression of 15-LOX2 is lost in all prostate cancer cell lines, accompanied by decreased enzymatic activity revealed by liquid chromatography/tandem mass spectrometry analyses. Further experiments show that the loss of 15-LOX2 expression results from transcriptional repression caused by mechanism(s) other than promoter hypermethylation or histone deacetylation. Subsequent functional studies indicate the following: 1) the 15-LOX2 product, 15(S)-hydroxyeicosatetraenoic acid, inhibits prostate cancer cell cycle progression; 2) 15-LOX2 expression in primary prostate epithelial cells is inversely correlated with cell cycle; and 3) restoration of 15-LOX2 expression in prostate cancer cells partially inhibits cell cycle progression. Taken together, these results suggest that 15-LOX2 could be a suppressor of prostate cancer development, which functions by restricting cell cycle progression.
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pubmed:grant |
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:BhatiaBobbyB,
pubmed-author:ChandraDhyanD,
pubmed-author:ChopraDharamD,
pubmed-author:ChungLeland W KLW,
pubmed-author:FischerSusan MSM,
pubmed-author:KleinRussell DRD,
pubmed-author:LiuJunweiJ,
pubmed-author:MaldonadoCarlos JCJ,
pubmed-author:NewmanRobert ARA,
pubmed-author:ShenJianjunJ,
pubmed-author:TangDean GDG,
pubmed-author:TangShaohuaS,
pubmed-author:TraagJeanineJ,
pubmed-author:YangPeiyingP,
pubmed-author:ZhauHaiyen EHE
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pubmed:issnType |
Print
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pubmed:day |
3
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
16189-201
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11839751-Alternative Splicing,
pubmed-meshheading:11839751-Amino Acid Sequence,
pubmed-meshheading:11839751-Arachidonate 15-Lipoxygenase,
pubmed-meshheading:11839751-Base Sequence,
pubmed-meshheading:11839751-Cell Cycle,
pubmed-meshheading:11839751-Cell Transformation, Neoplastic,
pubmed-meshheading:11839751-Cells, Cultured,
pubmed-meshheading:11839751-Cloning, Molecular,
pubmed-meshheading:11839751-DNA Primers,
pubmed-meshheading:11839751-Epithelial Cells,
pubmed-meshheading:11839751-Genetic Variation,
pubmed-meshheading:11839751-Genetic Vectors,
pubmed-meshheading:11839751-Humans,
pubmed-meshheading:11839751-Hydroxyeicosatetraenoic Acids,
pubmed-meshheading:11839751-Kinetics,
pubmed-meshheading:11839751-Male,
pubmed-meshheading:11839751-Molecular Sequence Data,
pubmed-meshheading:11839751-Prostate,
pubmed-meshheading:11839751-Prostatic Neoplasms,
pubmed-meshheading:11839751-RNA, Messenger,
pubmed-meshheading:11839751-Recombinant Proteins,
pubmed-meshheading:11839751-Reference Values,
pubmed-meshheading:11839751-Sequence Alignment,
pubmed-meshheading:11839751-Sequence Homology, Amino Acid,
pubmed-meshheading:11839751-Transcription, Genetic
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pubmed:year |
2002
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pubmed:articleTitle |
Evidence that arachidonate 15-lipoxygenase 2 is a negative cell cycle regulator in normal prostate epithelial cells.
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pubmed:affiliation |
Department of Carcinogenesis, the University of Texas MD Anderson Cancer Center, Science Park Research Division, Smithville, Texas 78957, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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