Linked Life Data

16302003

Source:http://linkedlifedata.com/resource/pubmed/id/16302003

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-2-3
pubmed:abstractText
Rhabdoid tumors (RTs) are aggressive and currently incurable pediatric malignancies. INI1/hSNF5 is a tumor suppressor biallelically inactivated in RTs. Our previous studies have indicated that cyclin D1 is a key downstream target of INI1/hSNF5 and genesis and/or survival of RTs in vivo is critically dependent on the presence of cyclin D1. In this report, we have tested the hypothesis that therapeutic targeting of cyclin D1 is an effective means of treating RTs. We found that RNA interference of cyclin D1 in rhabdoid cells was sufficient to induce G1 arrest and apoptosis. Furthermore, we found that pharmacological intervention with low micromolar concentrations of N-(4-hydroxyphenyl)retinamide (4-HPR), which downmodulates cyclin D1, induced G1 arrest and apoptosis in rhabdoid cell lines. 4-HPR in combination with 4-hydroxy-tamoxifen (4OH-Tam), synergistically inhibited survival as well as anchorage-dependent and -independent growth of rhabdoid cells and caused synergistic induction of cell cycle arrest and apoptosis. 4-HPR and tamoxifen exhibited synergistic growth inhibition of RTs in xenograft models in vivo. The effects of combination of drugs were correlated to the depletion of cyclin D1 levels both in in vitro and in vivo tumor models. These results demonstrate that 4-HPR and tamoxifen are effective chemotherapeutic agents for RTs. We propose that downmodulation of cyclin D1 is a novel and effective therapeutic strategy for RTs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
722-34
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Targeting cyclin D1, a downstream effector of INI1/hSNF5, in rhabdoid tumors.
pubmed:affiliation
Department of Molecular Genetics, Albert Einstein College of Medicine, New York, NY, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural