The SWI/SNF ATPases Are Required for Triple Negative Breast Cancer Cell Proliferation

Qiong Wu, Pasil Madany, Jacqueline Akech, Jason R. Dobson, Stephen Douthwright, Gillian Browne, Jennifer L. Colby, Georg E. Winter, James E. Bradner, Jitesh Pratap, Greenfield Sluder, Rohit Bhargava, Simion I. Chiosea, Andre J van Wijnen, Janet L. Stein, Gary S. Stein, Jane B. Lian, Jeffrey A. Nickerson, Anthony N. Imbalzano

Research output: Contribution to journalArticle

39 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2683-2694
Number of pages12
JournalJournal of Cellular Physiology
Volume230
Issue number11
DOIs
StatePublished - Nov 1 2015

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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    Wu, Q., Madany, P., Akech, J., Dobson, J. R., Douthwright, S., Browne, G., Colby, J. L., Winter, G. E., Bradner, J. E., Pratap, J., Sluder, G., Bhargava, R., Chiosea, S. I., van Wijnen, A. J., Stein, J. L., Stein, G. S., Lian, J. B., Nickerson, J. A., & Imbalzano, A. N. (2015). The SWI/SNF ATPases Are Required for Triple Negative Breast Cancer Cell Proliferation. Journal of Cellular Physiology, 230(11), 2683-2694. https://doi.org/10.1002/jcp.24991