Linked Life Data

19421142

Source:http://linkedlifedata.com/resource/pubmed/id/19421142

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2009-6-11
pubmed:abstractText
The development of chemoresistance represents a major obstacle in the successful treatment of cancers such as neuroblastoma (NB), a particularly aggressive childhood solid tumour. The mechanisms underlying the chemoresistant phenotype in NB were addressed by gene expression profiling of two doxorubicin (DoxR)-resistant vs sensitive parental cell lines. Not surprisingly, the MDR1 gene was included in the identified upregulated genes, although the highest overexpressed transcript in both cell lines was the frizzled-1 Wnt receptor (FZD1) gene, an essential component of the Wnt/beta-catenin pathway. FZD1 upregulation in resistant variants was shown to mediate sustained activation of the Wnt/beta-catenin pathway as revealed by nuclear beta-catenin translocation and target genes transactivation. Interestingly, specific micro-adapted short hairpin RNA (shRNAmir)-mediated FZD1 silencing induced parallel strong decrease in the expression of MDR1, another beta-catenin target gene, revealing a complex, Wnt/beta-catenin-mediated implication of FZD1 in chemoresistance. The significant restoration of drug sensitivity in FZD1-silenced cells confirmed the FZD1-associated chemoresistance. RNA samples from 21 patient tumours (diagnosis and postchemotherapy), showed a highly significant FZD1 and/or MDR1 overexpression after treatment, underlining a role for FZD1-mediated Wnt/beta-catenin pathway in clinical chemoresistance. Our data represent the first implication of the Wnt/beta-catenin pathway in NB chemoresistance and identify potential new targets to treat aggressive and resistant NB.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
11
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2245-56
pubmed:meshHeading
pubmed-meshheading:19421142-Active Transport, Cell Nucleus, pubmed-meshheading:19421142-Blotting, Western, pubmed-meshheading:19421142-Caspases, pubmed-meshheading:19421142-Cell Line, pubmed-meshheading:19421142-Cell Line, Tumor, pubmed-meshheading:19421142-Cell Nucleus, pubmed-meshheading:19421142-Cell Survival, pubmed-meshheading:19421142-Doxorubicin, pubmed-meshheading:19421142-Drug Resistance, Neoplasm, pubmed-meshheading:19421142-Female, pubmed-meshheading:19421142-Fluorescent Antibody Technique, pubmed-meshheading:19421142-Frizzled Receptors, pubmed-meshheading:19421142-Gene Expression Profiling, pubmed-meshheading:19421142-Gene Expression Regulation, Neoplastic, pubmed-meshheading:19421142-Humans, pubmed-meshheading:19421142-In Situ Hybridization, Fluorescence, pubmed-meshheading:19421142-Male, pubmed-meshheading:19421142-Neuroblastoma, pubmed-meshheading:19421142-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:19421142-P-Glycoprotein, pubmed-meshheading:19421142-RNA Interference, pubmed-meshheading:19421142-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:19421142-Signal Transduction, pubmed-meshheading:19421142-Wnt Proteins, pubmed-meshheading:19421142-beta Catenin
pubmed:year
2009
pubmed:articleTitle
The Wnt receptor FZD1 mediates chemoresistance in neuroblastoma through activation of the Wnt/beta-catenin pathway.
pubmed:affiliation
Department of Paediatrics, University Hospital CHUV, Lausanne, Switzerland. Marjorie.Flahaut@chuv.ch
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't