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BRG1 expression is increased in human glioma and controls glioma cell proliferation, migration and invasion in vitro

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Abstract

Purpose

The purposes of our study were to elucidate the role of BRG1 in the development of human glioma and to determine the effect of BRG1 on glioma cell growth, migration and invasion.

Methods

Using tissue microarray and immunohistochemistry, we evaluated BRG1 staining in 190 glioma tissues, 8 normal brain tissues and 8 tumor adjacent normal brain tissues. We studied glioma cell proliferative ability with reduced BRG1 expression by siRNA using CCK-8 cell proliferation assay and cell cycle analysis. We studied the role of BRG1 in glioma cell migration and invasion by cell migration assay and matrigel invasion assay. We performed western blot to detect cyclin D1, cyclin B1 and MMP-2 protein expression. We also detected MMP-2 enzyme activity by gelatin zymography.

Results

Our results showed that BRG1 expression was increased in benign tumor and malignant tumor compared with tumor adjacent normal brain tissue (P < 0.01 for both). We did not find any correlation between BRG1 expression and clinicopathological parameters. In addition, we found that knockdown of BRG1 in glioma cell lines inhibits cell growth due to the G1 phase arrest by downregulating cyclin D1. We further demonstrated that silencing of BRG1 in glioma cells inhibited the cell migration and invasion abilities, and downregulation of MMP-2 expression greatly contributed to the reduced cell invasion and migration abilities.

Conclusions

Our data indicated that BRG1 expression is significantly increased in human glioma and it may be involved in the process of glioma cell proliferation, migration and invasion.

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References

  • Asp P, Wihlborg M, Karlen M, Farrants AK (2002) Expression of BRG1, a human SWI/SNF component, affects the organisation of actin filaments through the RhoA signalling pathway. J Cell Sci 115(Pt 13):2735–2746

    Article  CAS  PubMed  Google Scholar 

  • Bai J, Zhang J, Wu J, Shen L, Zeng J, Ding J, Wu Y, Gong Z, Li A, Xu S, Zhou J, Li G (2010) JWA regulates melanoma metastasis by integrin alphaVbeta3 signaling. Oncogene 29(8):1227–1237. doi:10.1038/onc.2009.408

    Article  CAS  PubMed  Google Scholar 

  • Barcellos-Hoff MH, Newcomb EW, Zagzag D, Narayana A (2009) Therapeutic targets in malignant glioblastoma microenvironment. Semin Radiat Oncol 19(3):163–170. doi:10.1016/j.semradonc.2009.02.004

    Article  PubMed  PubMed Central  Google Scholar 

  • Becker TM, Haferkamp S, Dijkstra MK, Scurr LL, Frausto M, Diefenbach E, Scolyer RA, Reisman DN, Mann GJ, Kefford RF, Rizos H (2009) The chromatin remodelling factor BRG1 is a novel binding partner of the tumor suppressor p16INK4a. Mol Cancer 8:4. doi:10.1186/1476-4598-8-4

    Article  PubMed  PubMed Central  Google Scholar 

  • Biegel JA, Tan L, Zhang F, Wainwright L, Russo P, Rorke LB (2002) Alterations of the hSNF5/INI1 gene in central nervous system atypical teratoid/rhabdoid tumors and renal and extrarenal rhabdoid tumors. Clin Cancer Res 8(11):3461–3467

    CAS  PubMed  Google Scholar 

  • Brooks PC, Stromblad S, Sanders LC, von Schalscha TL, Aimes RT, Stetler-Stevenson WG, Quigley JP, Cheresh DA (1996) Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3. Cell 85(5):683–693. doi: S0092-8674(00)81235-0

    Article  CAS  PubMed  Google Scholar 

  • Carlson M, Osmond BC, Botstein D (1981) Mutants of yeast defective in sucrose utilization. Genetics 98(1):25–40

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Decristofaro MF, Betz BL, Rorie CJ, Reisman DN, Wang W, Weissman BE (2001) Characterization of SWI/SNF protein expression in human breast cancer cell lines and other malignancies. J Cell Physiol 186(1):136–145. doi:10.1002/1097-4652(200101)186:1<136:AID-JCP1010>3.0.CO;2-4

    Article  CAS  PubMed  Google Scholar 

  • Dinant C, Houtsmuller AB, Vermeulen W (2008) Chromatin structure and DNA damage repair. Epigenetics Chromatin 1(1):9. doi:10.1186/1756-8935-1-9

    Article  PubMed  PubMed Central  Google Scholar 

  • Flowers S, Nagl NG Jr, Beck GR Jr, Moran E (2009) Antagonistic roles for BRM and BRG1 SWI/SNF complexes in differentiation. J Biol Chem 284(15):10067–10075. doi:10.1074/jbc.M808782200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fukuoka J, Fujii T, Shih JH, Dracheva T, Meerzaman D, Player A, Hong K, Settnek S, Gupta A, Buetow K, Hewitt S, Travis WD, Jen J (2004) Chromatin remodeling factors and BRM/BRG1 expression as prognostic indicators in non-small cell lung cancer. Clin Cancer Res 10(13):4314–4324. doi:10.1158/1078-0432.CCR-03-0489

    Article  CAS  PubMed  Google Scholar 

  • Glaros S, Cirrincione GM, Muchardt C, Kleer CG, Michael CW, Reisman D (2007) The reversible epigenetic silencing of BRM: implications for clinical targeted therapy. Oncogene 26(49):7058–7066. doi:10.1038/sj.onc.1210514

    Article  CAS  PubMed  Google Scholar 

  • Grytsenko P, Ilina O, Friedl P (2011) Interstitial guidance of cancer invasion. J Pathol. doi:10.1002/path.3031

  • Hendricks KB, Shanahan F, Lees E (2004) Role for BRG1 in cell cycle control and tumor suppression. Mol Cell Biol 24(1):362–376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hill DA, Chiosea S, Jamaluddin S, Roy K, Fischer AH, Boyd DD, Nickerson JA, Imbalzano AN (2004) Inducible changes in cell size and attachment area due to expression of a mutant SWI/SNF chromatin remodeling enzyme. J Cell Sci 117(Pt 24):5847–5854. doi:10.1242/jcs.01502

    Article  CAS  PubMed  Google Scholar 

  • Kang H, Cui K, Zhao K (2004) BRG1 controls the activity of the retinoblastoma protein via regulation of p21CIP1/WAF1/SDI. Mol Cell Biol 24(3):1188–1199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Keenen B, Qi H, Saladi SV, Yeung M, de la Serna IL (2010) Heterogeneous SWI/SNF chromatin remodeling complexes promote expression of microphthalmia-associated transcription factor target genes in melanoma. Oncogene 29(1):81–92. doi:10.1038/onc.2009.304

    Article  CAS  PubMed  Google Scholar 

  • Lee MH, Yang HY (2003) Regulators of G1 cyclin-dependent kinases and cancers. Cancer Metastasis Rev 22(4):435–449

    Article  CAS  PubMed  Google Scholar 

  • Lin H, Wong RP, Martinka M, Li G (2010) BRG1 expression is increased in human cutaneous melanoma. Br J Dermatol 163(3):502–510. doi:10.1111/j.1365-2133.2010.09851.x

    Article  CAS  PubMed  Google Scholar 

  • Mei PJ, Bai J, Liu H, Li C, Wu YP, Yu ZQ, Zheng JN (2011) RUNX3 expression is lost in glioma and its restoration causes drastic suppression of tumor invasion and migration. J Cancer Res Clin Oncol. doi:10.1007/s00432-011-1063-4

  • Naidu SR, Love IM, Imbalzano AN, Grossman SR, Androphy EJ (2009) The SWI/SNF chromatin remodeling subunit BRG1 is a critical regulator of p53 necessary for proliferation of malignant cells. Oncogene 28(27):2492–2501. doi:10.1038/onc.2009.121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ohgaki H, Kleihues P (2005) Epidemiology and etiology of gliomas. Acta Neuropathol 109(1):93–108. doi:10.1007/s00401-005-0991-y

    Article  PubMed  Google Scholar 

  • Overall CM, Kleifeld O (2006) Tumour microenvironment—opinion: validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy. Nat Rev Cancer 6(3):227–239. doi:10.1038/nrc1821

    Article  CAS  PubMed  Google Scholar 

  • Reardon DA, Desjardins A, Peters K, Gururangan S, Sampson J, Rich JN, McLendon R, Herndon JE II, Marcello J, Threatt S, Friedman AH, Vredenburgh JJ, Friedman HS (2011) Phase II study of metronomic chemotherapy with bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy. J Neurooncol 103(2):371–379. doi:10.1007/s11060-010-0403-6

    Article  CAS  PubMed  Google Scholar 

  • Reisman DN, Sciarrotta J, Wang W, Funkhouser WK, Weissman BE (2003) Loss of BRG1/BRM in human lung cancer cell lines and primary lung cancers: correlation with poor prognosis. Cancer Res 63(3):560–566

    CAS  PubMed  Google Scholar 

  • Reisman D, Glaros S, Thompson EA (2009) The SWI/SNF complex and cancer. Oncogene 28(14):1653–1668. doi:10.1038/onc.2009.4

    Article  CAS  PubMed  Google Scholar 

  • Saladi SV, Keenen B, Marathe HG, Qi H, Chin KV, de la Serna IL (2010) Modulation of extracellular matrix/adhesion molecule expression by BRG1 is associated with increased melanoma invasiveness. Mol Cancer 9:280. doi:10.1186/1476-4598-9-280

    Article  PubMed  PubMed Central  Google Scholar 

  • Sentani K, Oue N, Kondo H, Kuraoka K, Motoshita J, Ito R, Yokozaki H, Yasui W (2001) Increased expression but not genetic alteration of BRG1, a component of the SWI/SNF complex, is associated with the advanced stage of human gastric carcinomas. Pathobiology 69(6):315–320

    Article  CAS  PubMed  Google Scholar 

  • Simone C (2006) SWI/SNF: the crossroads where extracellular signaling pathways meet chromatin. J Cell Physiol 207(2):309–314. doi:10.1002/jcp.20514

    Article  CAS  PubMed  Google Scholar 

  • Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996. doi:10.1056/NEJMoa043330

    Article  CAS  PubMed  Google Scholar 

  • Sun A, Tawfik O, Gayed B, Thrasher JB, Hoestje S, Li C, Li B (2007) Aberrant expression of SWI/SNF catalytic subunits BRG1/BRM is associated with tumor development and increased invasiveness in prostate cancers. Prostate 67(2):203–213. doi:10.1002/pros.20521

    Article  CAS  PubMed  Google Scholar 

  • Wang W, Xue Y, Zhou S, Kuo A, Cairns BR, Crabtree GR (1996) Diversity and specialization of mammalian SWI/SNF complexes. Genes Dev 10(17):2117–2130

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Sansam CG, Thom CS, Metzger D, Evans JA, Nguyen PT, Roberts CW (2009) 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 69(20):8094–8101. doi:10.1158/0008-5472.CAN-09-0733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wong AK, Shanahan F, Chen Y, Lian L, Ha P, Hendricks K, Ghaffari S, Iliev D, Penn B, Woodland AM, Smith R, Salada G, Carillo A, Laity K, Gupte J, Swedlund B, Tavtigian SV, Teng DH, Lees E (2000) BRG1, a component of the SWI-SNF complex, is mutated in multiple human tumor cell lines. Cancer Res 60(21):6171–6177

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This project is supported by grants from the National Natural Science Foundation of China (No. 30972976, 81071854), the Science and Technology Department of Jiangsu province (No. BK2009089) and Xuzhou Medical College (No. 2010KJZ03, 2010KJZ04).

Conflict of interest

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

  1. Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, 221002, China

    Jin Bai & Jun-Nian Zheng

  2. Department of Neurosurgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu Province, China

    Peng-Jin Mei & Zheng-Quan Yu

  3. School of Pathology, Xuzhou Medical College, Xuzhou, 221002, China

    Hui Liu & Yong-Ping Wu

  4. The First Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221002, China

    Hui Liu, Chen Li, Wang Li & Jun-Nian Zheng

  5. Laboratory of Biological Cancer Therapy, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu Province, China

    Jun-Nian Zheng

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  1. Jin Bai
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Corresponding authors

Correspondence to Zheng-Quan Yu or Jun-Nian Zheng.

Additional information

Jin Bai and Peng-Jin Mei contributed equally to this paper.

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Bai, J., Mei, PJ., Liu, H. et al. BRG1 expression is increased in human glioma and controls glioma cell proliferation, migration and invasion in vitro. J Cancer Res Clin Oncol 138, 991–998 (2012). https://doi.org/10.1007/s00432-012-1172-8

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  • DOI: https://doi.org/10.1007/s00432-012-1172-8

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