LEANNA BROOKS BRG1: LUNG CANCER. LUNG CANCER WHAT DOES THIS HAVE TO DO WITH BRG1? LOH in chromosome 19 is frequent in NSLC tumors BRG1 is very frequently.

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Presentation transcript:

LEANNA BROOKS BRG1: LUNG CANCER

LUNG CANCER

WHAT DOES THIS HAVE TO DO WITH BRG1? LOH in chromosome 19 is frequent in NSLC tumors BRG1 is very frequently inactivated in lung tumors. (as many as 1/3 of NSCLC cell lines have mutations in BRG1) Mutations include frameshifts, nonsense or missense mutations. Patients whose tumors are missing BRG1 have a worse prognosis BRG1 mutations have also been found in pancreatic, prostate, breast and colon cancer cell lines The mutations result in a truncated protein

SWI/SNF CHROMATIN REMODELING COMPLEX Activates (or deactivates) transcription by changing the structure of chromosomes; changing their affinity for transcription factors ATP dependent Critical for differentiation and proliferation BRG1 is the ATPase – it provides the energy needed to carry out this function

MOUSE EXPERIMENTS Cre-Pos (black) = BRG1 inactivated Cre-Neg (white) = control Heterozygotes show more tumors, while homozygotes for BRG1 inactivation do not Heterozygote inactivation of BRG1 leads to larger tumors (and worse prognosis)

BRG1 DOWN-REGULATES MYC

RESOURCES Fukuoka, J, Fujii,T, Shih, JH, et al. (2004). “Chromatin Remodeling Factors and BRM/BRG1 Expression as Prognostic Indicators in Non-Small Cell Lung Cancer.” Clinical Cancer Research, 10: Glaros, S, Cirrincione, GM, Palanca, A, et al. (2008). “Targeted Knockout of BRG1 Potentiates Lung Cancer Development”. The Journal of Cancer Research, 68: “Non-Small Cell Lung Cancer Treatment” National Cancer Institute. Web. 26 Mar Reisman, D, and Thompson, EA. (2009). “The SWI/SNF complex and cancer”. Oncogene: 28, Rodrigues-Nieto, S, and Sanchez-Cespedes, M. (2009). “BRG1 and LKB1: tales of two tumor suppressor genes on chromosome 19p and lung cancer”. Carcinogenesis: 30, Romero, OA, Setien, F, John, S, et al. (2012). “The tumor suppressor and chromatin- remodeling factor BRG1 antagonizes Myc activity and promotes cell differentiation in human cancer”. EMBO Molecular Medicine, 4: “What are the key statistics about lung cancer”. Web. 15 Mar Wu, JI. (2012). “Diverse functions of ATP-dependent chromatin remodeling complexes in development and cancer.” Acta Biochimica Biophys Sin, 44: