Title
The SWI/SNF ATPases Are Required for Triple Negative Breast Cancer Cell Proliferation
UMMS Affiliation
Department of Cell and Developmental Biology
Publication Date
11-1-2015
Document Type
Article
Disciplines
Cancer Biology | Cell Biology | Cellular and Molecular Physiology
Abstract
The Brahma (BRM) and Brahma-related Gene 1 (BRG1) ATPases are highly conserved homologs that catalyze the chromatin remodeling functions of the multi-subunit human SWI/SNF chromatin remodeling enzymes in a mutually exclusive manner. SWI/SNF enzyme subunits are mutated or missing in many cancer types, but are overexpressed without apparent mutation in other cancers. Here, we report that both BRG1 and BRM are overexpressed in most primary breast cancers independent of the tumor's receptor status. Knockdown of either ATPase in a triple negative breast cancer cell line reduced tumor formation in vivo and cell proliferation in vitro. Fewer cells in S phase and an extended cell cycle progression time were observed without any indication of apoptosis, senescence, or alterations in migration or attachment properties. Combined knockdown of BRM and BRG1 showed additive effects in the reduction of cell proliferation and time required for completion of cell cycle, suggesting that these enzymes promote cell cycle progression through independent mechanisms. Knockout of BRG1 or BRM using CRISPR/Cas9 technology resulted in the loss of viability, consistent with a requirement for both enzymes in triple negative breast cancer cells.
DOI of Published Version
10.1002/jcp.24991
Source
J Cell Physiol. 2015 Nov;230(11):2683-94. doi: 10.1002/jcp.24991. Link to article on publisher's site
Journal/Book/Conference Title
Journal of cellular physiology
Related Resources
PubMed ID
25808524
Repository Citation
Wu, Qiong; Madany, Pasil A.; Akech, Jacqueline; Dobson, Jason; Douthwright, Stephen; Browne, Gillian; Colby, Jennifer L.; Winter, Georg E.; Bradner, James E.; Pratap, Jitesh; Sluder, Greenfield; Bhargava, Rohit; Chiosea, Simion I.; Van Wijnen, Andre J.; Stein, Janet L.; Stein, Gary S.; Lian, Jane B.; Nickerson, Jeffrey A.; and Imbalzano, Anthony N., "The SWI/SNF ATPases Are Required for Triple Negative Breast Cancer Cell Proliferation" (2015). Cell and Developmental Biology Publications. 155.
https://escholarship.umassmed.edu/cellbiology_pp/155