title: Loss of the SWI/SNF ATPase subunits BRM and BRG1 drives lung cancer development.
abstract: Inactivation ofBrg1andBrmaccelerated lung tumor development, shortened tumor latency, and caused a loss of differentiation. Tumors with Brg1 and/or Brm loss recapitulated the evolution of human lung cancer as observed by the development of local tumor invasion as well as distal tumor metastasis, thereby making this model useful in lung cancer studies. Brg1 loss contributed to metastasis in part by driving E-cadherin loss and Vimentin up-regulation. By changing more than 6% of the murine genome with the down-regulation of tumor suppressors, DNA repair, differentiation and cell adhesion genes, and the concomitant up-regulation of oncogenes, angiogenesis, metastasis and antiapoptosis genes, caused by the dual loss of Brg1/Brm further accelerated tumor development. Additionally, this Brg1/Brm-driven change in gene expression resulted in a nearly two-fold increase in tumorigenicity in Brg1/Brm knockout mice compared with wild type mice. Most importantly, Brg1/Brm-driven lung cancer development histologically and clinically reflects human lung cancer development thereby making this GEMM model potentially useful.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Florida, Florida, USA.
authors.forename: Stefanie B
authors.initials: SB
authors.lastname: Marquez-Vilendrer
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Florida, Florida, USA.
authors.forename: Sudhir K
authors.initials: SK
authors.lastname: Rai
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Florida, Florida, USA.
authors.forename: Sarah Jb
authors.initials: SJ
authors.lastname: Gramling
authors.affiliation: Department of Pathology, University of Florida, Florida, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Lu
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Florida, Florida, USA.
authors.forename: David N
authors.initials: DN
authors.lastname: Reisman
keywords: lung cancer; smarca2; smarca4; swi/snf; tumor