Linked Life Data

11973649

Source:http://linkedlifedata.com/resource/pubmed/id/11973649

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2002-4-25
pubmed:abstractText
Ewing's sarcoma (EWS) cells contain levels of poly(ADP-ribose) polymerase (PARP) significantly higher than other eukaryotic cells. Previously, we cloned the PARP gene promoter region from EWS cells, showed that it contained multiple ETS-binding sites and demonstrated a positive regulation of PARP by ETS1. We now report that, contrary to ETS1, EWS/FLI-1, an aberrant ETS transcription factor present in most EWS cells, is a negative effector of PARP transcription. Because PARP levels have been associated with cellular resistance or sensitivity to genotoxic agents, we studied the effect of modifying PARP levels in EWS cells on their response to DNA damage by modulating the expression of ETS1 or EWS/FLI-1 using antisense methodology. Results show that stable down-regulation of ETS1 increases the resistance of EWS cells to various genotoxic agents, whereas down-regulation of EWS/FLI-1 has pro-apoptotic effects. Because down-regulation EWS/FLI-1 does not dramatically change PARP levels, these results suggest a direct effect for EWS/FLI-1 in the DNA damage response of EWS cells. Since expression of the aberrant fusion proteins by EWS cells is essential for maintaining their neoplastic phenotype, our results suggest that the use of antisense oligonucleotides in combination with chemotherapeutic agents or radiation may be doubly effective by causing both an increase in sensitivity to therapeutic agents and a simultaneous down-regulation, or reversion, of the neoplastic phenotype of EWS cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/ETS1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/EWS-FLI fusion protein, http://linkedlifedata.com/resource/pubmed/chemical/Etoposide, http://linkedlifedata.com/resource/pubmed/chemical/Nucleic Acid Synthesis Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins, Fusion, http://linkedlifedata.com/resource/pubmed/chemical/Poly(ADP-ribose) Polymerases, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Protein c-ets-1, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Protein c-fli-1, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-ets, http://linkedlifedata.com/resource/pubmed/chemical/RNA-Binding Protein EWS, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2890-5
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Differential regulation of the response to DNA damage in Ewing's sarcoma cells by ETS1 and EWS/FLI-1.
pubmed:affiliation
Department of Radiation Medicine, Vincent T. Lombardi Cancer Center, Georgetown University Medical Center, Washington DC 20007, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.