| pubmed-article:16740713 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:16740713 | lifeskim:mentions | umls-concept:C1519346 | lld:lifeskim |
| pubmed-article:16740713 | lifeskim:mentions | umls-concept:C0032405 | lld:lifeskim |
| pubmed-article:16740713 | lifeskim:mentions | umls-concept:C0215848 | lld:lifeskim |
| pubmed-article:16740713 | lifeskim:mentions | umls-concept:C0021467 | lld:lifeskim |
| pubmed-article:16740713 | lifeskim:mentions | umls-concept:C0017262 | lld:lifeskim |
| pubmed-article:16740713 | lifeskim:mentions | umls-concept:C0021469 | lld:lifeskim |
| pubmed-article:16740713 | lifeskim:mentions | umls-concept:C0332257 | lld:lifeskim |
| pubmed-article:16740713 | lifeskim:mentions | umls-concept:C1879547 | lld:lifeskim |
| pubmed-article:16740713 | pubmed:issue | 11 | lld:pubmed |
| pubmed-article:16740713 | pubmed:dateCreated | 2006-6-2 | lld:pubmed |
| pubmed-article:16740713 | pubmed:abstractText | Poly(ADP-ribose) polymerase (PARP)-1, an enzyme that catalyzes the attachment of ADP ribose to target proteins, acts as a component of enhancer/promoter regulatory complexes. In the present study, we show that pharmacologic inhibition of PARP-1 with 3,4-dihydro-5-[4-(1-piperidinyl)butoxyl]-1(2H)-isoquinolinone (DPQ) results in a strong delay in tumor formation and in a dramatic reduction in tumor size and multiplicity during 7,12-dimethylbenz(a)anthracene plus 12-O-tetradecanoylphorbol-13-acetate-induced skin carcinogenesis. This observation was parallel with a reduction in the skin inflammatory infiltrate in DPQ-treated mice and tumor vasculogenesis. Inhibition of PARP also affected activator protein-1 (AP-1) activation but not nuclear factor-kappaB (NF-kappaB). Using cDNA expression array analysis, a substantial difference in key tumor-related gene expression was found between chemically induced mice treated or not with PARP inhibitor and also between wild-type and parp-1 knockout mice. Most important differences were found in gene expression for Nfkbiz, S100a9, Hif-1alpha, and other genes involved in carcinogenesis and inflammation. These results were corroborated by real-time PCR. Moreover, the transcriptional activity of hypoxia-inducible factor-1alpha (HIF-1alpha) was compromised by PARP inhibition or in PARP-1-deficient cells, as measured by gene reporter assays and the expression of key target genes for HIF-1alpha. Tumor vasculature was also strongly inhibited in PARP-1-deficient mice and by DPQ. In summary, this study shows that inhibition of PARP on itself is able to control tumor growth, and PARP inhibition or genetic deletion of PARP-1 prevents from tumor promotion through their ability to cooperate with the activation AP-1, NF-kappaB, and HIF-1alpha. | lld:pubmed |
| pubmed-article:16740713 | pubmed:language | eng | lld:pubmed |
| pubmed-article:16740713 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16740713 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:16740713 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16740713 | pubmed:month | Jun | lld:pubmed |
| pubmed-article:16740713 | pubmed:issn | 0008-5472 | lld:pubmed |
| pubmed-article:16740713 | pubmed:author | pubmed-author:VilluendasRaq... | lld:pubmed |
| pubmed-article:16740713 | pubmed:author | pubmed-author:OliverF... | lld:pubmed |
| pubmed-article:16740713 | pubmed:author | pubmed-author:Ruiz de... | lld:pubmed |
| pubmed-article:16740713 | pubmed:author | pubmed-author:Aguilar-Quesa... | lld:pubmed |
| pubmed-article:16740713 | pubmed:author | pubmed-author:PirisMiguel... | lld:pubmed |
| pubmed-article:16740713 | pubmed:author | pubmed-author:Martin-OlivaD... | lld:pubmed |
| pubmed-article:16740713 | pubmed:author | pubmed-author:O'valleFranci... | lld:pubmed |
| pubmed-article:16740713 | pubmed:author | pubmed-author:Muñoz-GámezJo... | lld:pubmed |
| pubmed-article:16740713 | pubmed:author | pubmed-author:Martínez-Rome... | lld:pubmed |
| pubmed-article:16740713 | pubmed:author | pubmed-author:García Del... | lld:pubmed |
| pubmed-article:16740713 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:16740713 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:16740713 | pubmed:volume | 66 | lld:pubmed |
| pubmed-article:16740713 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:16740713 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:16740713 | pubmed:pagination | 5744-56 | lld:pubmed |
| pubmed-article:16740713 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
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| pubmed-article:16740713 | pubmed:year | 2006 | lld:pubmed |
| pubmed-article:16740713 | pubmed:articleTitle | Inhibition of poly(ADP-ribose) polymerase modulates tumor-related gene expression, including hypoxia-inducible factor-1 activation, during skin carcinogenesis. | lld:pubmed |
| pubmed-article:16740713 | pubmed:affiliation | Institute of Parasitology and Biomedicine, Consejo Superior de Investigaciones Cientificas, Granada, Spain. | lld:pubmed |
| pubmed-article:16740713 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:16740713 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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