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dc.contributor.authorWu, Qiong
dc.contributor.authorSharma, Soni
dc.contributor.authorCui, Hang
dc.contributor.authorLeBlanc, Scott E.
dc.contributor.authorZhang, Hong
dc.contributor.authorMuthuswami, Rohini
dc.contributor.authorNickerson, Jeffrey A.
dc.contributor.authorImbalzano, Anthony N.
dc.date2022-08-11T08:08:03.000
dc.date.accessioned2022-08-23T15:40:52Z
dc.date.available2022-08-23T15:40:52Z
dc.date.issued2016-03-25
dc.date.submitted2016-05-31
dc.identifier.citation<p>Oncotarget. 2016 Mar 25. doi: 10.18632/oncotarget.8384. <a href="http://dx.doi.org/10.18632/oncotarget.8384">Link to article on publisher's site</a></p>
dc.identifier.issn1949-2553 (Linking)
dc.identifier.doi10.18632/oncotarget.8384
dc.identifier.pmid27029062
dc.identifier.urihttp://hdl.handle.net/20.500.14038/26496
dc.description.abstractBrahma related gene product 1 (BRG1) is an ATPase that drives the catalytic activity of a subset of the mammalian SWI/SNF chromatin remodeling enzymes. BRG1 is overexpressed in most human breast cancer tumors without evidence of mutation and is required for breast cancer cell proliferation. We demonstrate that knockdown of BRG1 sensitized triple negative breast cancer cells to chemotherapeutic drugs used to treat breast cancer. An inhibitor of the BRG1 bromodomain had no effect on breast cancer cell viability, but an inhibitory molecule that targets the BRG1 ATPase activity recapitulated the increased drug efficacy observed in the presence of BRG1 knockdown. We further demonstrate that inhibition of BRG1 ATPase activity blocks the induction of ABC transporter genes by these chemotherapeutic drugs and that BRG1 binds to ABC transporter gene promoters. This inhibition increased intracellular concentrations of the drugs, providing a likely mechanism for the increased chemosensitivity. Since ABC transporters and their induction by chemotherapy drugs are a major cause of chemoresistance and treatment failure, these results support the idea that targeting the enzymatic activity of BRG1 would be an effective adjuvant therapy for breast cancer.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=27029062&dopt=Abstract">Link to Article in PubMed</a>
dc.rights<p>All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License. </p>
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/
dc.subjectepigenetics
dc.subjectBRG1
dc.subjectSWI/SNF
dc.subjectbreast cancer
dc.subjectdrug transporters
dc.subjectCancer Biology
dc.subjectCell Biology
dc.titleTargeting the chromatin remodeling enzyme BRG1 increases the efficacy of chemotherapy drugs in breast cancer cells
dc.typeJournal Article
dc.source.journaltitleOncotarget
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1180&amp;context=cellbiology_pp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/cellbiology_pp/181
dc.identifier.contextkey8667037
refterms.dateFOA2022-08-23T15:40:52Z
html.description.abstract<p>Brahma related gene product 1 (BRG1) is an ATPase that drives the catalytic activity of a subset of the mammalian SWI/SNF chromatin remodeling enzymes. BRG1 is overexpressed in most human breast cancer tumors without evidence of mutation and is required for breast cancer cell proliferation. We demonstrate that knockdown of BRG1 sensitized triple negative breast cancer cells to chemotherapeutic drugs used to treat breast cancer. An inhibitor of the BRG1 bromodomain had no effect on breast cancer cell viability, but an inhibitory molecule that targets the BRG1 ATPase activity recapitulated the increased drug efficacy observed in the presence of BRG1 knockdown. We further demonstrate that inhibition of BRG1 ATPase activity blocks the induction of ABC transporter genes by these chemotherapeutic drugs and that BRG1 binds to ABC transporter gene promoters. This inhibition increased intracellular concentrations of the drugs, providing a likely mechanism for the increased chemosensitivity. Since ABC transporters and their induction by chemotherapy drugs are a major cause of chemoresistance and treatment failure, these results support the idea that targeting the enzymatic activity of BRG1 would be an effective adjuvant therapy for breast cancer.</p>
dc.identifier.submissionpathcellbiology_pp/181
dc.contributor.departmentUMass Metabolic Network
dc.contributor.departmentDepartment of Cell and Developmental Biology


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