UMMS Affiliation

Department of Cell and Developmental Biology

Date

3-25-2016

Document Type

Article

Abstract

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.

Rights and Permissions

Citation: Oncotarget. 2016 Mar 25. doi: 10.18632/oncotarget.8384. Link to article on publisher's site

All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.

Related Resources

Link to Article in PubMed

Keywords

epigenetics, BRG1, SWI/SNF, breast cancer, drug transporters

Journal Title

Oncotarget

PubMed ID

27029062

Creative Commons License


This work is licensed under a Creative Commons Attribution 3.0 License.

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