Download BRG1: Lung Cancer

BRG1: LUNG CANCER
LEANNA BROOKS
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: 4314-4324.
• Glaros, S, Cirrincione, GM, Palanca, A, et al. (2008). “Targeted Knockout of BRG1
Potentiates Lung Cancer Development”. The Journal of Cancer Research, 68: 36893696.
• “Non-Small Cell Lung Cancer Treatment” National Cancer Institute. Web. 26 Mar.
2015. <http://www.cancer.gov/cancertopics/pdq/treatment/non-small-celllung/Patient/page4>.
• Reisman, D, and Thompson, EA. (2009). “The SWI/SNF complex and cancer”.
Oncogene: 28, 1653-1668.
• 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,
547-554.
• Romero, OA, Setien, F, John, S, et al. (2012). “The tumor suppressor and chromatinremodeling factor BRG1 antagonizes Myc activity and promotes cell differentiation
in human cancer”. EMBO Molecular Medicine, 4: 603-616.
• “What are the key statistics about lung cancer”. Web. 15 Mar. 2015. < http://
www.cancer.org/cancer/lungcancer-non-smallcell/detailedguide/non-small-celllung-cancer-key-statistics>.
• Wu, JI. (2012). “Diverse functions of ATP-dependent chromatin remodeling
complexes in development and cancer.” Acta Biochimica Biophys Sin, 44: 54-69.