Source:http://linkedlifedata.com/resource/pubmed/id/17354225
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2007-4-30
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pubmed:abstractText |
The pro-inflammatory cytokine, tumour necrosis factor-alpha, TNF-alpha, is dysregulated in malignant compared with normal ovarian surface epithelium (OSE). Several epidemiological studies have associated inflammation with ovarian tumorigenesis, with TNF-alpha playing a key role in modulating invasion, angiogenesis and metastasis. Here, we show that TNF-alpha also induces expression of arate-limiting enzyme in arginine synthesis, argininosuccinate synthetase (AS), thereby linking inflammation with several arginine-dependent metabolic pathways, implicated in accelerated carcinogenesis and tumour progression. Having identified AS mRNA induction in TNF-alpha-treated IGROV-1 ovarian cancer cells, using RNA-arbitrarily primed-PCR, we then observed differential regulation of AS mRNA and protein in malignant, compared with normal, OSE cells. A cDNA cancer profiling array with matched normal ovarian and ovarian tumour samples revealed increased expression of AS mRNA in the latter. Moreover, AS protein co-localised with TNF-alpha in ovarian cancer cells, with significantly higher levels of AS in malignant compared with normal ovarian tissue. Increased co-expression of AS and TNF-alpha mRNA was also observed in 2 other epithelial tumours, non-small cell lung and stomach cancer, compared with normal corresponding tissues. In summary, high levels of AS expression, which may be required for several arginine-dependent processes in cancer, including the production of nitric oxide, proline, pyrimidines and polyamines, is regulated by TNF-alpha and may provide an important molecular pathway linking inflammation and metabolism to ovarian tumorigenesis.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0020-7136
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
121
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6-11
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pubmed:dateRevised |
2007-7-24
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pubmed:meshHeading |
pubmed-meshheading:17354225-Argininosuccinate Synthase,
pubmed-meshheading:17354225-Epithelial Cells,
pubmed-meshheading:17354225-Female,
pubmed-meshheading:17354225-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:17354225-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:17354225-Health,
pubmed-meshheading:17354225-Humans,
pubmed-meshheading:17354225-Ovarian Neoplasms,
pubmed-meshheading:17354225-RNA, Messenger,
pubmed-meshheading:17354225-Tumor Cells, Cultured,
pubmed-meshheading:17354225-Tumor Necrosis Factor-alpha
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pubmed:year |
2007
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pubmed:articleTitle |
Aberrant regulation of argininosuccinate synthetase by TNF-alpha in human epithelial ovarian cancer.
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pubmed:affiliation |
Cancer Research UK, Translational Oncology Laboratory, Barts and The London, Queen Mary's School of Medicine and Dentistry, London, United Kingdom. peter.szlosarek@bartsandthelondon.nhs.uk
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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