Cancer Research AACR Legacy EMT and Cancer Progression and Treatment
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wong, A. K. C.
Right arrow Articles by Lees, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wong, A. K. C.
Right arrow Articles by Lees, E.
[Cancer Research 60, 6171-6177, November 1, 2000]
© 2000 American Association for Cancer Research

Tumor Biology

BRG1, a Component of the SWI-SNF Complex, Is Mutated in Multiple Human Tumor Cell Lines

Alexander K. C. Wong1, Frances Shanahan, Yuan Chen, Lubing Lian, Phuong Ha, Kristin Hendricks, Siavash Ghaffari, Diana Iliev, Brandon Penn, Anne-Marie Woodland, Richard Smith, Grant Salada, Arlene Carillo, Kirsten Laity, Jamila Gupte, Brad Swedlund, Sean V. Tavtigian, David H-F. Teng2,3 and Emma Lees2,4

Myriad Genetics, Inc., Salt Lake City, Utah 84108 [A. K. C. W., Y. C., L. L., P. H., S. G., D. I., B. P., A-M. W., R. S., G. S., A. C., K. L., J. G., B. S., S. V. T., D. H-F. T.], and DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304 [F. S., K. H., E. L.]

Human BRG1 is a component of the evolutionarily conserved SWI-SNF chromatin remodeling complex. BRG1 has been implicated in growth control through its interaction with the tumor suppressor pRb and may consequently serve as a negative regulator of proliferation. Postulating that BRG1 may itself be a tumor suppressor gene, we screened a panel of tumor cell lines to determine whether the gene is targeted for mutation. We report that the COOH-terminal region of BRG1 is homozygously deleted in two carcinoma cell lines, prostate TSU-Pr1 and lung A-427. In addition, biallelic inactivations of BRG1 were observed in four other cell lines derived from carcinomas of the breast, lung, pancreas, and prostate; their mutations in BRG1 included three frameshift lesions and one nonsense lesion. Point mutations were also discovered in a number of other cell lines, however in most cases any effect of these mutations on BRG1 function remains to be established. A variety of different mutations within BRG1, in several cell lines, suggest that BRG1 may be targeted for disruption in human tumors. Significantly, reintroduction of BRG1 into cells lacking BRG1 expression was sufficient to reverse their transformed phenotype inducing growth arrest and a flattened morphology. These data strongly support the model that BRG1 may function as a tumor suppressor and strengthen the hypothesis that the regulation of gene expression through chromatin remodeling is critical for cancer progression. It will be important to confirm these observations in primary tumors.




This article has been cited by other articles:


Home page
 Cancer Res.Home page
B. Weissman and K. E. Knudsen
Hijacking the Chromatin Remodeling Machinery: Impact of SWI/SNF Perturbations in Cancer
Cancer Res., November 1, 2009; 69(21): 8223 - 8230.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
X. Wang, C. G. Sansam, C. S. Thom, D. Metzger, J. A. Evans, P. T.L. Nguyen, and C. W.M. Roberts
Oncogenesis Caused by Loss of the SNF5 Tumor Suppressor Is Dependent on Activity of BRG1, the ATPase of the SWI/SNF Chromatin Remodeling Complex
Cancer Res., October 15, 2009; 69(20): 8094 - 8101.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
H. Lin, R. P.C. Wong, M. Martinka, and G. Li
Loss of SNF5 Expression Correlates with Poor Patient Survival in Melanoma
Clin. Cancer Res., October 15, 2009; 15(20): 6404 - 6411.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
S. B. Kutluay, S. L. DeVos, J. E. Klomp, and S. J. Triezenberg
Transcriptional Coactivators Are Not Required for Herpes Simplex Virus Type 1 Immediate-Early Gene Expression In Vitro
J. Virol., April 15, 2009; 83(8): 3436 - 3449.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
S. Rodriguez-Nieto and M. Sanchez-Cespedes
BRG1 and LKB1: tales of two tumor suppressor genes on chromosome 19p and lung cancer
Carcinogenesis, April 1, 2009; 30(4): 547 - 554.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
E. S. McKenna, C. G. Sansam, Y.-J. Cho, H. Greulich, J. A. Evans, C. S. Thom, L. A. Moreau, J. A. Biegel, S. L. Pomeroy, and C. W. M. Roberts
Loss of the Epigenetic Tumor Suppressor SNF5 Leads to Cancer without Genomic Instability
Mol. Cell. Biol., October 15, 2008; 28(20): 6223 - 6233.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. J.-C. Sheu, J. H. Choi, I. Yildiz, F.-J. Tsai, Y. Shaul, T.-L. Wang, and I.-M. Shih
The Roles of Human Sucrose Nonfermenting Protein 2 Homologue in the Tumor-Promoting Functions of Rsf-1
Cancer Res., June 1, 2008; 68(11): 4050 - 4057.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
W. Xia, S. Nagase, A. G. Montia, S. M. Kalachikov, M. Keniry, T. Su, L. Memeo, H. Hibshoosh, and R. Parsons
BAF180 Is a Critical Regulator of p21 Induction and a Tumor Suppressor Mutated in Breast Cancer
Cancer Res., March 15, 2008; 68(6): 1667 - 1674.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Xu, J. Zhang, and X. Chen
The Activity of p53 Is Differentially Regulated by Brm- and Brg1-containing SWI/SNF Chromatin Remodeling Complexes
J. Biol. Chem., December 28, 2007; 282(52): 37429 - 37435.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
B. A. McKinley and M. V. Sukhodolets
Escherichia coli RNA polymerase-associated SWI/SNF protein RapA: evidence for RNA-directed binding and remodeling activity
Nucleic Acids Res., December 18, 2007; 35(21): 7044 - 7060.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
N. Yamamichi, K.-i. Inada, M. Ichinose, M. Yamamichi-Nishina, T. Mizutani, H. Watanabe, K. Shiogama, M. Fujishiro, T. Okazaki, N. Yahagi, et al.
Frequent Loss of Brm Expression in Gastric Cancer Correlates with Histologic Features and Differentiation State
Cancer Res., November 15, 2007; 67(22): 10727 - 10735.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
J. Zhang, T. Ohta, A. Maruyama, T. Hosoya, K. Nishikawa, J. M. Maher, S. Shibahara, K. Itoh, and M. Yamamoto
BRG1 Interacts with Nrf2 To Selectively Mediate HO-1 Induction in Response to Oxidative Stress
Mol. Cell. Biol., November 1, 2006; 26(21): 7942 - 7952.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
S. Bilodeau, S. Vallette-Kasic, Y. Gauthier, D. Figarella-Branger, T. Brue, F. Berthelet, A. Lacroix, D. Batista, C. Stratakis, J. Hanson, et al.
Role of Brg1 and HDAC2 in GR trans-repression of the pituitary POMC gene and misexpression in Cushing disease.
Genes & Dev., October 15, 2006; 20(20): 2871 - 2886.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Coisy-Quivy, O. Disson, V. Roure, C. Muchardt, J.-M. Blanchard, and J.-C. Dantonel
Role for brm in cell growth control.
Cancer Res., May 15, 2006; 66(10): 5069 - 5076.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
H. Liu, N. Mulholland, H. Fu, and K. Zhao
Cooperative Activity of BRG1 and Z-DNA Formation in Chromatin Remodeling.
Mol. Cell. Biol., April 1, 2006; 26(7): 2550 - 2559.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
A. Klochendler-Yeivin, E. Picarsky, and M. Yaniv
Increased DNA Damage Sensitivity and Apoptosis in Cells Lacking the Snf5/Ini1 Subunit of the SWI/SNF Chromatin Remodeling Complex.
Mol. Cell. Biol., April 1, 2006; 26(7): 2661 - 2674.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. Datta, S. Majumder, S. Bai, K. Ghoshal, H. Kutay, D. S. Smith, J. W. Crabb, and S. T. Jacob
Physical and Functional Interaction of DNA Methyltransferase 3A with Mbd3 and Brg1 in Mouse Lymphosarcoma Cells
Cancer Res., December 1, 2005; 65(23): 10891 - 10900.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
S. J. Bultman, T. C. Gebuhr, and T. Magnuson
A Brg1 mutation that uncouples ATPase activity from chromatin remodeling reveals an essential role for SWI/SNF-related complexes in {beta}-globin expression and erythroid development
Genes & Dev., December 1, 2005; 19(23): 2849 - 2861.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
N. G. Nagl Jr., A. Patsialou, D. S. Haines, P. B. Dallas, G. R. Beck Jr., and E. Moran
The p270 (ARID1A/SMARCF1) Subunit of Mammalian SWI/SNF-Related Complexes Is Essential for Normal Cell Cycle Arrest
Cancer Res., October 15, 2005; 65(20): 9236 - 9244.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
I.-M. Shih, J. J.-C. Sheu, A. Santillan, K. Nakayama, M. J. Yen, R. E. Bristow, R. Vang, G. Parmigiani, R. J. Kurman, C. G. Trope, et al.
Amplification of a chromatin remodeling gene, Rsf-1/HBXAP, in ovarian carcinoma
PNAS, September 27, 2005; 102(39): 14004 - 14009.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
L. Wang, R. A. Baiocchi, S. Pal, G. Mosialos, M. Caligiuri, and S. Sif
The BRG1- and hBRM-Associated Factor BAF57 Induces Apoptosis by Stimulating Expression of the Cylindromatosis Tumor Suppressor Gene
Mol. Cell. Biol., September 15, 2005; 25(18): 7953 - 7965.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
C. L. Smith and C. L. Peterson
A Conserved Swi2/Snf2 ATPase Motif Couples ATP Hydrolysis to Chromatin Remodeling
Mol. Cell. Biol., July 15, 2005; 25(14): 5880 - 5892.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
R. J. Gibbons
Histone modifying and chromatin remodelling enzymes in cancer and dysplastic syndromes
Hum. Mol. Genet., April 15, 2005; 14(suppl_1): R85 - R92.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
P. P. Medina, J. Carretero, E. Ballestar, B. Angulo, F. Lopez-Rios, M. Esteller, and M. Sanchez-Cespedes
Transcriptional targets of the chromatin-remodelling factor SMARCA4/BRG1 in lung cancer cells
Hum. Mol. Genet., April 1, 2005; 14(7): 973 - 982.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
D. A. Hill, S. Chiosea, S. Jamaluddin, K. Roy, A. H. Fischer, D. D. Boyd, J. A. Nickerson, and A. N. Imbalzano
Inducible changes in cell size and attachment area due to expression of a mutant SWI/SNF chromatin remodeling enzyme
J. Cell Sci., November 15, 2004; 117(24): 5847 - 5854.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Z. Ma, M. J. Chang, R. Shah, J. Adamski, X. Zhao, and E. N. Benveniste
Brg-1 Is Required for Maximal Transcription of the Human Matrix Metalloproteinase-2 Gene
J. Biol. Chem., October 29, 2004; 279(44): 46326 - 46334.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
A. H. Lund and M. van Lohuizen
Epigenetics and cancer
Genes & Dev., October 1, 2004; 18(19): 2315 - 2335.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
C. B. Zraly, D. R. Marenda, and A. K. Dingwall
SNR1 (INI1/SNF5) Mediates Important Cell Growth Functions of the Drosophila Brahma (SWI/SNF) Chromatin Remodeling Complex
Genetics, September 1, 2004; 168(1): 199 - 214.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Medjkane, E. Novikov, I. Versteege, and O. Delattre
The Tumor Suppressor hSNF5/INI1 Modulates Cell Growth and Actin Cytoskeleton Organization
Cancer Res., May 15, 2004; 64(10): 3406 - 3413.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
M. Hirano, Y. Kikuchi, S. Nisitani, A. Yamaguchi, A. Satoh, T. Ito, H. Iba, and K. Takatsu
Bruton's tyrosine kinase (Btk) enhances transcriptional co-activation activity of BAM11, a Btk-associated molecule of a subunit of SWI/SNF complexes
Int. Immunol., May 1, 2004; 16(5): 747 - 757.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Muller, C. F. Calkhoven, X. Sha, and A. Leutz
The CCAAT Enhancer-binding Protein {alpha} (C/EBP{alpha}) Requires a SWI/SNF Complex for Proliferation Arrest
J. Biol. Chem., February 20, 2004; 279(8): 7353 - 7358.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
I. Oruetxebarria, F. Venturini, T. Kekarainen, A. Houweling, L. M. P. Zuijderduijn, A. Mohd-Sarip, R. G. J. Vries, R. C. Hoeben, and C. P. Verrijzer
p16INK4a Is Required for hSNF5 Chromatin Remodeler-induced Cellular Senescence in Malignant Rhabdoid Tumor Cells
J. Biol. Chem., January 30, 2004; 279(5): 3807 - 3816.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
K. B. Hendricks, F. Shanahan, and E. Lees
Role for BRG1 in Cell Cycle Control and Tumor Suppression
Mol. Cell. Biol., January 1, 2004; 24(1): 362 - 376.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. Vernell, K. Helin, and H. Muller
Identification of Target Genes of the p16INK4A-pRB-E2F Pathway
J. Biol. Chem., November 14, 2003; 278(46): 46124 - 46137.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
S. Pal, R. Yun, A. Datta, L. Lacomis, H. Erdjument-Bromage, J. Kumar, P. Tempst, and S. Sif
mSin3A/Histone Deacetylase 2- and PRMT5-Containing Brg1 Complex Is Involved in Transcriptional Repression of the Myc Target Gene cad
Mol. Cell. Biol., November 1, 2003; 23(21): 7475 - 7487.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. W. Marshall, K. A. Link, C. E. Petre-Draviam, and K. E. Knudsen
Differential Requirement of SWI/SNF for Androgen Receptor Activity
J. Biol. Chem., August 15, 2003; 278(33): 30605 - 30613.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Z. Nie, Z. Yan, E. H. Chen, S. Sechi, C. Ling, S. Zhou, Y. Xue, D. Yang, D. Murray, E. Kanakubo, et al.
Novel SWI/SNF Chromatin-Remodeling Complexes Contain a Mixed-Lineage Leukemia Chromosomal Translocation Partner
Mol. Cell. Biol., April 15, 2003; 23(8): 2942 - 2952.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. N. Reisman, J. Sciarrotta, W. Wang, W. K. Funkhouser, and B. E. Weissman
Loss of BRG1/BRM in Human Lung Cancer Cell Lines and Primary Lung Cancers: Correlation with Poor Prognosis
Cancer Res., February 1, 2003; 63(3): 560 - 566.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Roy, I. L. de la Serna, and A. N. Imbalzano
The Myogenic Basic Helix-Loop-Helix Family of Transcription Factors Shows Similar Requirements for SWI/SNF Chromatin Remodeling Enzymes during Muscle Differentiation in Culture
J. Biol. Chem., September 6, 2002; 277(37): 33818 - 33824.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
R. Mudhasani and J. D. Fontes
The Class II Transactivator Requires brahma-Related Gene 1 To Activate Transcription of Major Histocompatibility Complex Class II Genes
Mol. Cell. Biol., July 15, 2002; 22(14): 5019 - 5026.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Mizutani, T. Ito, M. Nishina, N. Yamamichi, A. Watanabe, and H. Iba
Maintenance of Integrated Proviral Gene Expression Requires Brm, a Catalytic Subunit of SWI/SNF Complex
J. Biol. Chem., May 3, 2002; 277(18): 15859 - 15864.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
H. R. Moinova, W.-D. Chen, L. Shen, D. Smiraglia, J. Olechnowicz, L. Ravi, L. Kasturi, L. Myeroff, C. Plass, R. Parsons, et al.
HLTF gene silencing in human colon cancer
PNAS, April 2, 2002; 99(7): 4562 - 4567.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
K. E. Neely, A. H. Hassan, C. E. Brown, L. Howe, and J. L. Workman
Transcription Activator Interactions with Multiple SWI/SNF Subunits
Mol. Cell. Biol., March 15, 2002; 22(6): 1615 - 1625.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. W. Strobeck, D. N. Reisman, R. W. Gunawardena, B. L. Betz, S. P. Angus, K. E. Knudsen, T. F. Kowalik, B. E. Weissman, and E. S. Knudsen
Compensation of BRG-1 Function by Brm. INSIGHT INTO THE ROLE OF THE CORE SWI{middle dot}SNF SUBUNITS IN RETINOBLASTOMA TUMOR SUPPRESSOR SIGNALING
J. Biol. Chem., February 8, 2002; 277(7): 4782 - 4789.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Kato, A. Tjernberg, W. Zhang, A. N. Krutchinsky, W. An, T. Takeuchi, Y. Ohtsuki, S. Sugano, D. R. de Bruijn, B. T. Chait, et al.
SYT Associates with Human SNF/SWI Complexes and the C-terminal Region of Its Fusion Partner SSX1 Targets Histones
J. Biol. Chem., February 8, 2002; 277(7): 5498 - 5505.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
P. Asp, M. Wihlborg, M. Karlen, and A.-K. O. Farrants
Expression of BRG1, a human SWI/SNF component, affects the organisation of actin filaments through the RhoA signalling pathway
J. Cell Sci., January 7, 2002; 115(13): 2735 - 2746.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
C. J. Guidi, A. T. Sands, B. P. Zambrowicz, T. K. Turner, D. A. Demers, W. Webster, T. W. Smith, A. N. Imbalzano, and S. N. Jones
Disruption of Ini1 Leads to Peri-Implantation Lethality and Tumorigenesis in Mice
Mol. Cell. Biol., May 15, 2001; 21(10): 3598 - 3603.
[Abstract] [Full Text]

Home page
 Proc. Natl. Acad. Sci. USAHome page
H. R. Moinova, W.-D. Chen, L. Shen, D. Smiraglia, J. Olechnowicz, L. Ravi, L. Kasturi, L. Myeroff, C. Plass, R. Parsons, et al.
HLTF gene silencing in human colon cancer
PNAS, April 2, 2002; 99(7): 4562 - 4567.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2000 by the American Association for Cancer Research.