Linked Life Data

17616514

Source:http://linkedlifedata.com/resource/pubmed/id/17616514

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2007-9-14
pubmed:abstractText
Although cure rate of childhood acute lymphoblastic leukemia (ALL) has surpassed 80%, drug resistance remains a major cause of treatment failure. We previously identified a panel of 33 genes differentially expressed in prednisolone sensitive versus resistant ALL cells from newly diagnosed children. Here we used bioinformatics to identify resistance genes most likely to contain single nucleotide polymorphisms (SNPs) in their promoter region. The highest priority gene was SMARCB1, a core member of the SWI/SNF complex which promotes glucocorticoid effects through nucleosome remodeling. We identified several SNPs in the SMARCB1 promoter in lymphoblastoid cells from 90 individuals in the Centre d'Etude du Polymorphisme Humain (CEPH) panel. Among these SNPs, the -228G>T SNP (allele frequency 9.4%) was the only one that significantly increased reporter activity in human ALL cell lines. Furthermore, we identified nuclear protein poly (ADP-ribose) polymerase family, member 1 (PARP1) as a nuclear protein binding to the SMARCB1 promoter and showed that the -228 SNP significantly altered PARP1 binding affinity. The -228G>T SNP altered SMARCB1 mRNA and protein levels and a positive association was found between the SMARCB1 mRNA level and both the -228 genotype and prednisolone sensitivity in CEPH cell lines. Finally, knockdown experiments performed in human ALL cell lines confirmed that lower SMARCB1 expression increased prednisolone resistance. In summary, we provide functional evidence that SMARCB1 is involved in prednisolone resistance and identified a promoter SNP that alters the level of SMARCB1 mRNA and protein expression and the binding of PARP1 to the SMARCB1 promoter.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2261-71
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:17616514-Amino Acid Sequence, pubmed-meshheading:17616514-Blotting, Western, pubmed-meshheading:17616514-Cell Line, pubmed-meshheading:17616514-Chromosomal Proteins, Non-Histone, pubmed-meshheading:17616514-Chromosome Mapping, pubmed-meshheading:17616514-DNA-Binding Proteins, pubmed-meshheading:17616514-Electrophoretic Mobility Shift Assay, pubmed-meshheading:17616514-Gene Expression, pubmed-meshheading:17616514-Gene Frequency, pubmed-meshheading:17616514-Genotype, pubmed-meshheading:17616514-Humans, pubmed-meshheading:17616514-Lymphocytes, pubmed-meshheading:17616514-Molecular Sequence Data, pubmed-meshheading:17616514-Mutagenesis, Site-Directed, pubmed-meshheading:17616514-Poly(ADP-ribose) Polymerases, pubmed-meshheading:17616514-Polymorphism, Single Nucleotide, pubmed-meshheading:17616514-Prednisolone, pubmed-meshheading:17616514-Promoter Regions, Genetic, pubmed-meshheading:17616514-Protein Binding, pubmed-meshheading:17616514-RNA, Messenger, pubmed-meshheading:17616514-RNA, Small Interfering, pubmed-meshheading:17616514-RNA Interference, pubmed-meshheading:17616514-Sequence Alignment, pubmed-meshheading:17616514-Spectrometry, Mass, Matrix-Assisted Laser..., pubmed-meshheading:17616514-Steroids, pubmed-meshheading:17616514-Transcription Factors
pubmed:year
2007
pubmed:articleTitle
Expression of SMARCB1 modulates steroid sensitivity in human lymphoblastoid cells: identification of a promoter SNP that alters PARP1 binding and SMARCB1 expression.
pubmed:affiliation
Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural