Abstract IA02: Dissection of the BRG1 and MYC/MAX biological connection and its use in lung cancer therapeutics

Lung cancer is the first cause of death due to cancer in most western countries, in part because of the low efficacy of most current therapies. In this regard, understanding the genetic architecture of lung malignancies has proven to constitute a reliable strategy to develop novel anticancer agents and foretell response to therapies. Previously, we reported that one third of the lung tumors of the non-small cell lung cancer type (NSCLC) endure inactivation of BRG1, which constitutes the fourth most commonly altered gene in this type of cancer. Interestingly, we also observed that BRG1 inactivation and MYC amplification are mutually exclusive events in lung cancer, supporting previous observations of a functional relationship between the MYC and BRG1 proteins. The BRG1 gene codes for a member of the SWI/SNF chromatin remodeling complex, and its role in cancer development is still poorly understood, which hinders its potential use in clinical settings.Here, I report our discovery on how the expression of wild type BRG1 in lung cancer cells up-regulates lung-specific transcripts, significantly restoring the gene expression signature of normal lung. Using cell lines from several cancer types we found that those lacking BRG1 do not respond to retinoic acid (RA) or glucocorticoids (GC), while restoration of BRG1 restitutes sensitivity, as determined by changes in cell morphology and gene expression. Conversely, in SH-SY5Y cells, a paradigm of RA-dependent differentiation, abrogatio...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Myc in Human Cancers: Oral Presentations - Invited Abstracts Source Type: research