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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2001-3-13
pubmed:abstractText
We have previously demonstrated that the activation of p53 signaling may contribute to tumor growth inhibition by the CRE-decoy oligonucleotide containing CRE sequence (5'-TGACGTCA-3') (Lee et al., Biochemistry 39, 4863-4868, 2000). However, growth inhibition by CRE-decoy treatment was also observed in tumor cells containing a mutant p53 (Park et al., J. Biol. Chem. 274, 1573-1580, 1999). To understand additional mechanisms of the decoy oligonucleotide, we investigated the effect on cyclin D1 expression and a cyclin D1/Cdk4/retinoblastoma protein (pRB) signaling pathway. Here we show that in MCF7 breast cancer cells the CRE-decoy competed with cyclin D1-CRE (5'-TAACGTCA-3') for binding transcription factors and reduced cyclin D1 gene expression (in reporter gene assay, Northern blotting and Western blotting) to modulate cyclin D1/Cdk4/pRB signaling and G1-S progression in a steady state and/or under estrogen stimulation. Decrease of cyclin D1 protein level by CRE-decoy treatment was also observed in p53-mutated cancer cells. Cyclin D1 expression was also diminished in MCF7 cells stably expressing dominant negative mutant CREB indicating that the nonspecific effect of oligonucleotide or its degradation products could be excluded. These data suggest that inhibition of cyclin D1 expression contributes to the growth inhibition induced by the decoy oligonucleotide in MCF7 cells through a cyclin D1/Cdk4/pRB signaling pathway. Downregulation of cyclin D1 expression also provides a mechanism of CRE-decoy-induced growth inhibition in tumor cells having p53 mutation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-291X
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Academic Press.
pubmed:issnType
Print
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1213-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11243864-Breast Neoplasms, pubmed-meshheading:11243864-Cell Division, pubmed-meshheading:11243864-Cyclic AMP Response Element-Binding Protein, pubmed-meshheading:11243864-Cyclin D1, pubmed-meshheading:11243864-Cyclin-Dependent Kinase 4, pubmed-meshheading:11243864-Cyclin-Dependent Kinases, pubmed-meshheading:11243864-Estrogens, pubmed-meshheading:11243864-Female, pubmed-meshheading:11243864-Humans, pubmed-meshheading:11243864-Oligonucleotides, pubmed-meshheading:11243864-Promoter Regions, Genetic, pubmed-meshheading:11243864-Proto-Oncogene Proteins, pubmed-meshheading:11243864-RNA, Messenger, pubmed-meshheading:11243864-Response Elements, pubmed-meshheading:11243864-Retinoblastoma Protein, pubmed-meshheading:11243864-Signal Transduction, pubmed-meshheading:11243864-Transcriptional Activation, pubmed-meshheading:11243864-Transfection, pubmed-meshheading:11243864-Tumor Cells, Cultured
pubmed:year
2001
pubmed:articleTitle
Reduction in cyclin D1/Cdk4/retinoblastoma protein signaling by CRE-decoy oligonucleotide.
pubmed:affiliation
Department of Biochemistry, Korea University College of Medicine, Seoul, 136-701, Korea. parkyg@korea.ac.kr
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't