Abstract 602: Silencing BRG1 in human cancers

Abstract BRG1 is a novel tumor suppressor that serves as the major catalytic subunit of the SWI/SNF complex. Because this complex is central to the function of a number of transcription factors and key cellular proteins and it is required for a plethora of signal transduction pathways, its loss can have devastating effects on cellular function. We know that BRG1 is not only lost in lung cancer but also in a variety of tumor types: between 10-40%. Hence, the loss of this protein plays an important role in cancer development and progression. In cell lines, it has been well document that BRG1 is mutated or altered in the vast majority of cell lines, but in primary lung cancer mutations are not found. Our analysis has led us to believe that BRG1 is epigenetically silenced like its homolog BRM. Hence, it may be possible to restore its expression in cancer cells. The loss of BRG1 impacts the sensitivity to Cisplatin by making cells more sensitive to the DNA damaging effects of this agent. Similarly, this loss also impacts sensitivity to EGFR inhibitors by making cells more resistant. Hence, the loss of BRG1 can help to explain the reciprocal sensitivity to these drugs seen in cancers. Hence, the BRG1 protein can play the role of a biomarker for chemotherapy sensitivity as well as being a potential target for therapy. Further research will reveal how this gene can best be integrated into clinical practice. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 602. doi:10.1158/1538-7445.AM2011-602