Knockdown of either ATPase in triple-negative breast cancer cell lines reduced cell proliferation in vitro and tumor formation in xenografts. An extended cell cycle progression time was observed without apoptosis, without senescence, or without alterations in migration or attachment. Combined knockdown of BRM and BRG1 produced additive effects, suggesting that these enzymes function, at least in part, through independent mechanisms. Knockout of BRG1 or BRM using CRISPR/Cas9 technology caused cell death. Our work supports the novel idea that overexpression of BRG1 and BRM is common in breast cancer and that BRG1 and BRM are required for breast cancer cell proliferation and survival. These results are in direct contrast to other tumors where BRG1 acts as a tumor suppressor (79). For example, it is mutated in lung and other cancers. We and others have now shown that BRG1 is upregulated but rarely mutated in primary breast and prostate tumors, in melanoma and neuroblastoma, and in pancreatic, gastric, and colorectal carcinomas (51–60, 80).
