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Chunk #9 — BRG1 is Necessary for Fatty Acid Biosynthesis in Support of Proliferation in Breast Cancer

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Mammalian SWI/SNF Enzymes and the Epigenetics of Tumor Cell Metabolic Reprogramming.
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We first reported that the alternative SWI/SNF chromatin remodeling enzyme ATPases BRG1 and BRM are required for proliferation of breast cancer cells (59). Western blots of biopsies showed that BRG1 protein levels were higher in tumor than in normal tissue. Analysis of TCGA Breast Cancer patient data revealed an approximate twofold increase in BRG1 mRNA levels (64) and in BRG1 protein levels (78) in tumors compared to normal tissue across all subtypes. These are not well-controlled comparisons because of the great heterogeneity in normal tissue cell types. More convincingly, immunohistochemistry confirmed that the BRG1 and BRM proteins are greatly overexpressed in most primary breast cancers independent of receptor status (55, 59). BRG1 staining was rarely observed in the normal ductal epithelial cells from which most breast tumors derive but was seen in normal myoepithelial cells. However, in tumors BRG1 staining was observed in almost every cell. Because of the heterogeneity of breast cancer subtypes our further experimental work focused on triple-negative breast cancer, the most aggressive and deadly type.