| pubmed-article:16949053 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:16949053 | lifeskim:mentions | umls-concept:C0025914 | lld:lifeskim |
| pubmed-article:16949053 | lifeskim:mentions | umls-concept:C0026809 | lld:lifeskim |
| pubmed-article:16949053 | lifeskim:mentions | umls-concept:C0029016 | lld:lifeskim |
| pubmed-article:16949053 | lifeskim:mentions | umls-concept:C0009375 | lld:lifeskim |
| pubmed-article:16949053 | lifeskim:mentions | umls-concept:C0079419 | lld:lifeskim |
| pubmed-article:16949053 | lifeskim:mentions | umls-concept:C1155874 | lld:lifeskim |
| pubmed-article:16949053 | pubmed:issue | 8 | lld:pubmed |
| pubmed-article:16949053 | pubmed:dateCreated | 2006-9-19 | lld:pubmed |
| pubmed-article:16949053 | pubmed:abstractText | The p53 tumor suppressor protein is sequence-normal in azoxymethane (AOM)-induced mouse colon tumors, making them a good model for human colon cancers that retain a wild type p53 gene. Cellular localization and co-immunoprecipitation experiments using a cell line derived from an AOM-induced colon tumor (AJ02-NM(0) cells) pointed to constitutively expressed Mdm2 as being an important negative regulator of p53 in these cells. Although the Mdm2 inhibitory protein p19/ARF was expressed in AJ02-NM(0) cells, its level of expression was not sufficient for p53 activation. We tested the response of AJ02-NM(0) cells to the recently developed Mdm2 inhibitor, Nutlin-3. Nutlin-3 was found to activate p53 DNA binding in AJ02-NM(0) cells, to a level comparable to doxorubicin and 5-fluorouracil (5-FU). In addition, Nutlin-3 increased expression of the p53 target genes Bax and PERP to a greater extent than doxorubicin or 5-FU, and triggered a G2/M phase arrest in these cells, compared to a G1 arrest triggered by doxorubicin and 5-FU. The differences in the cellular response may be related to differences in the kinetics of p53 activation and/or its post-translational modification status. In an ex vivo experiment, Nutlin-3 was found to activate p53 target gene expression and apoptosis in AOM-induced tumor tissue, but not in normal adjacent mucosa. Our data indicate that Mdm2 inhibitors may be an effective means of selectively targeting colon cancers that retain a sequence-normal p53 gene while sparing normal tissue and that the AOM model is an appropriate model for the preclinical development of these drugs. | lld:pubmed |
| pubmed-article:16949053 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16949053 | pubmed:language | eng | lld:pubmed |
| pubmed-article:16949053 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16949053 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:16949053 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16949053 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16949053 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16949053 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16949053 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16949053 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16949053 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16949053 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16949053 | pubmed:month | Oct | lld:pubmed |
| pubmed-article:16949053 | pubmed:issn | 0006-2952 | lld:pubmed |
| pubmed-article:16949053 | pubmed:author | pubmed-author:NambiarPrasha... | lld:pubmed |
| pubmed-article:16949053 | pubmed:author | pubmed-author:GiardinaCharl... | lld:pubmed |
| pubmed-article:16949053 | pubmed:author | pubmed-author:AizuWataruW | lld:pubmed |
| pubmed-article:16949053 | pubmed:author | pubmed-author:RosenbergDani... | lld:pubmed |
| pubmed-article:16949053 | pubmed:author | pubmed-author:BelinskyGlenn... | lld:pubmed |
| pubmed-article:16949053 | pubmed:author | pubmed-author:ChenBenB | lld:pubmed |
| pubmed-article:16949053 | pubmed:author | pubmed-author:FlynnChristop... | lld:pubmed |
| pubmed-article:16949053 | pubmed:author | pubmed-author:NoonanEmily... | lld:pubmed |
| pubmed-article:16949053 | pubmed:author | pubmed-author:BoesColleen... | lld:pubmed |
| pubmed-article:16949053 | pubmed:author | pubmed-author:GodmanCassand... | lld:pubmed |
| pubmed-article:16949053 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:16949053 | pubmed:day | 16 | lld:pubmed |
| pubmed-article:16949053 | pubmed:volume | 72 | lld:pubmed |
| pubmed-article:16949053 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:16949053 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:16949053 | pubmed:pagination | 981-91 | lld:pubmed |
| pubmed-article:16949053 | pubmed:dateRevised | 2007-11-14 | lld:pubmed |
| pubmed-article:16949053 | pubmed:meshHeading | pubmed-meshheading:16949053... | lld:pubmed |
| pubmed-article:16949053 | pubmed:meshHeading | pubmed-meshheading:16949053... | lld:pubmed |
| pubmed-article:16949053 | pubmed:meshHeading | pubmed-meshheading:16949053... | lld:pubmed |
| pubmed-article:16949053 | pubmed:meshHeading | pubmed-meshheading:16949053... | lld:pubmed |
| pubmed-article:16949053 | pubmed:meshHeading | pubmed-meshheading:16949053... | lld:pubmed |
| pubmed-article:16949053 | pubmed:meshHeading | pubmed-meshheading:16949053... | lld:pubmed |
| pubmed-article:16949053 | pubmed:meshHeading | pubmed-meshheading:16949053... | lld:pubmed |
| pubmed-article:16949053 | pubmed:meshHeading | pubmed-meshheading:16949053... | lld:pubmed |
| pubmed-article:16949053 | pubmed:meshHeading | pubmed-meshheading:16949053... | lld:pubmed |
| pubmed-article:16949053 | pubmed:meshHeading | pubmed-meshheading:16949053... | lld:pubmed |
| pubmed-article:16949053 | pubmed:meshHeading | pubmed-meshheading:16949053... | lld:pubmed |
| pubmed-article:16949053 | pubmed:meshHeading | pubmed-meshheading:16949053... | lld:pubmed |
| pubmed-article:16949053 | pubmed:meshHeading | pubmed-meshheading:16949053... | lld:pubmed |
| pubmed-article:16949053 | pubmed:meshHeading | pubmed-meshheading:16949053... | lld:pubmed |
| pubmed-article:16949053 | pubmed:year | 2006 | lld:pubmed |
| pubmed-article:16949053 | pubmed:articleTitle | Circumvention and reactivation of the p53 oncogene checkpoint in mouse colon tumors. | lld:pubmed |
| pubmed-article:16949053 | pubmed:affiliation | Department of Molecular & Cell Biology, 91 North Eagleville Road, University of Connecticut, Storrs, CT 06269-3125, USA. | lld:pubmed |
| pubmed-article:16949053 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:16949053 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| pubmed-article:16949053 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:16949053 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:16949053 | lld:pubmed |
