SALL4, a Stem Cell Factor, Affects the Side Population by Regulation of the ATP-Binding Cassette Drug Transport Genes

DSpace/Manakin Repository

SALL4, a Stem Cell Factor, Affects the Side Population by Regulation of the ATP-Binding Cassette Drug Transport Genes

Show simple item record

dc.contributor.author Cui, Wei
dc.contributor.author Lu, Jiayun
dc.contributor.author He, Jie
dc.contributor.author Guo, Ye
dc.contributor.author Liu, Bee H.
dc.contributor.author Jeong, Ha-Won
dc.contributor.author Yang, Yang
dc.contributor.author Li, Lingling
dc.contributor.author Song, David
dc.contributor.author Chai, Li
dc.date.accessioned 2011-12-06T02:52:19Z
dc.date.issued 2011
dc.identifier.citation Jeong, Ha-Won, Wei Cui, Youyang Yang, Jiayun Lu, Jie He, Ailing Li, David Song, Ye Guo, Bee H. Liu, and Li Chai. 2011. SALL4, a stem cell factor, affects the side population by regulation of the ATP-binding cassette drug transport genes. PLoS ONE 6(4): e18372. en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:5360616
dc.description.abstract Our previous work shows that the stem cell factor SALL4 plays a central role in embryonic and leukemic stem cells. In this study, we report that SALL4 expression was higher in drug resistant primary acute myeloid leukemic patients than those from drug-responsive cases. In addition, while overexpression of SALL4 led to drug resistance in cell lines, cells with decreased SALL4 expression were more sensitive to drug treatments than the parental cells. This led to our investigation of the implication of SALL4 in drug resistance and its role in side population (SP) cancer stem cells. SALL4 expression was higher in SP cells compared to non-SP cells by 2–4 fold in various malignant hematopoietic cell lines. Knocking down of SALL4 in isolated SP cells resulted in a reduction of SP cells, indicating that SALL4 is required for their self-renewal. The SP phenotype is known to be mediated by members of the ATP-binding cassette (ABC) drug transport protein family, such as ABCG2 and ABCA3. Using chromatin-immunoprecipitation (ChIP), quantitative reverse transcription polymerase chain reaction (qRT-PCR) and electrophoretic mobility shift assay(EMSA), we demonstrated that SALL4 was able to bind to the promoter region of ABCA3 and activate its expression while regulating the expression of ABCG2 indirectly. Furthermore, SALL4 expression was positively correlated to those of ABCG2 and ABCA3 in primary leukemic patient samples. Taken together, our results suggest a novel role for SALL4 in drug sensitivity, at least in part through the maintenance of SP cells, and therefore may be responsible for drug-resistance in leukemia. We are the first to demonstrate a direct link between stem cell factor SALL4, SP and drug resistance in leukemia. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pone.0018372 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079717/pdf/ en_US
dash.license LAA
dc.subject genetics en_US
dc.subject DNA-binding proteins en_US
dc.subject gene expression en_US
dc.subject hematopoietic stem cells en_US
dc.subject hematologic cancers and related disorders en_US
dc.subject leukemias en_US
dc.subject cancers and neoplasms en_US
dc.title SALL4, a Stem Cell Factor, Affects the Side Population by Regulation of the ATP-Binding Cassette Drug Transport Genes en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS ONE en_US
dash.depositing.author Jeong, Ha-Won
dc.date.available 2011-12-06T02:52:19Z
dash.affiliation.other HMS^Pathology en_US
dash.affiliation.other HMS^Microbiology and Molecular Genetics en_US
dash.affiliation.other HMS^Population Medicine en_US
dash.affiliation.other HMS^Pathology en_US

Files in this item

Files Size Format View
3079717.pdf 768.9Kb PDF View/Open

This item appears in the following Collection(s)

Show simple item record

 
 

Search DASH


Advanced Search
 
 

Submitters