Skip to main content

Advertisement

SpringerLink
Log in

Quantitative expression analysis of apoptotic/antiapoptotic genes and association with immunolocalization of BAX and BCL-2 in peripheral and central giant cell lesions of the jaws

  • Research Article
  • Published:
Tumor Biology

Abstract

Central giant cell lesion (CGCL) and peripheral giant cell lesion (PGCL) of the jaws are characterized by multinucleated osteoclast-like giant cells in a background of mononuclear cells. While mononuclear cells retain proliferative activity in both lesions, giant cells are Ki-67 negative. This observation raised the theory that giant cells are formed by cytoplasmic fusion of mononuclear cells, and also that these lesions are of reactive nature. As the giant cells are not proliferating in CGCL and PGCL, apoptosis of such cells should be investigated. We investigated the transcription of BAX and BCL-2 mRNAs in six fresh samples of CGCL and six fresh samples of PGCL by qRT-PCR (quantitative reverse transcription PCR) and used immunohistochemistry to demonstrate the localization of these proteins, as well as caspase 3 active in six paraffin-embedded samples of CGCL and nine paraffin-embedded samples of PGCL. While both groups showed increased expression of BAX and BCL-2 mRNA, PGCL showed a higher apoptotic index (ratio BAX/BCL-2) than CGCL. The three proteins investigated were expressed almost exclusively in the cytoplasm of giant cells. To further confirm apoptotic activity, we performed TUNEL analysis in the same samples of the immunohistochemistry and found a higher positivity in the giant cells of PGCL compared to the giant cells of CGCL. Our results show increased expression of apoptotic-related genes in both PGCL and CGCL and that the giant cells are probably the main source of these events. Also, it raises a hypothesis that differences in the apoptotic activity might be associated with the different clinical behavior of CGCL and PGCL.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Kruse-Losler B, Diallo R, Gaertner C, Mischke KL, Joos U, Kleinheinz J. Central giant cell granuloma of the jaws: a clinical, radiologic, and histopathologic study of 26 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101(3):346–54.

    Article  PubMed  Google Scholar 

  2. de Lange J, van den Akker HP, van den Berg H. Central giant cell granuloma of the jaw: a review of the literature with emphasis on therapy options. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;104(5):603–15.

    Article  PubMed  Google Scholar 

  3. Horner K. Central giant cell granuloma of the jaws: a clinico-radiological study. Clin Radiol. 1989;40(6):622–6.

    Article  PubMed  CAS  Google Scholar 

  4. Katsikeris N, Kakarantza-Angelopoulou E, Angelopoulos AP. Peripheral giant cell granuloma. Clinicopathologic study of 224 new cases and review of 956 reported cases. Int J Oral Maxillofac Surg. 1988;17(2):94–9.

    Article  PubMed  CAS  Google Scholar 

  5. Itonaga I, Hussein I, Kudo O, et al. Cellular mechanisms of osteoclast formation and lacunar resorption in giant cell granuloma of the jaw. J Oral Pathol Med. 2003;32(4):224–31.

    Article  PubMed  CAS  Google Scholar 

  6. Souza PE, Mesquita RA, Gomez RS. Evaluation of p53, PCNA, Ki-67, MDM2 and AgNOR in oral peripheral and central giant cell lesions. Oral Dis. 2000;6(1):35–9.

    Article  PubMed  CAS  Google Scholar 

  7. Mighell A. PCNA and p53. Eur J Canc B Oral Oncol. 1995;31B(6):403–4.

    Article  CAS  Google Scholar 

  8. O’Malley M, Pogrel MA, Stewart JC, Silva RG, Regezi JA. Central giant cell granulomas of the jaws: phenotype and proliferation-associated markers. J Oral Pathol Med. 1997;26(4):159–63.

    Article  PubMed  Google Scholar 

  9. Bonetti F, Pelosi G, Martignoni G, et al. Peripheral giant cell granuloma: evidence for osteoclastic differentiation. Oral Surg Oral Med Oral Pathol. 1990;70(4):471–5.

    Article  PubMed  CAS  Google Scholar 

  10. Amaral FR, Brito JA, Perdigao PF, et al. NFATc1 and TNFalpha expression in giant cell lesions of the jaws. J Oral Pathol Med. 2010;39(3):269–74.

    Article  PubMed  CAS  Google Scholar 

  11. Duarte AP, Gomes CC, Gomez RS, Amaral FR. Increased expression of NFATc1 in giant cell lesions of the jaws, cherubism and brown tumor of hyperparathyroidism. Oncology Letters. 2011; doi:10.3892/ol.2011.274.

  12. Sasi N, Hwang M, Jaboin J, Csiki I, Lu B. Regulated cell death pathways: new twists in modulation of BCL2 family function. Mol Canc Therapeut. 2009;8(6):1421–9.

    Article  CAS  Google Scholar 

  13. Certo M, Del Gaizo Moore V, Nishino M, et al. Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. Canc Cell. 2006;9(5):351–65.

    Article  CAS  Google Scholar 

  14. Antonsson B. Bax and other pro-apoptotic Bcl-2 family “killer-proteins” and their victim the mitochondrion. Cell Tissue Res. 2001;306(3):347–61.

    Article  PubMed  CAS  Google Scholar 

  15. Creagh EM, Martin SJ. Caspases: cellular demolition experts. Biochem Soc Trans. 2001;29(Pt 6):696–702.

    Article  PubMed  CAS  Google Scholar 

  16. Nicholson DW, Ali A, Thornberry NA, et al. Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature. 1995;376(6535):37–43.

    Article  PubMed  CAS  Google Scholar 

  17. Abdo EN, Alves LC, Rodrigues AS, Mesquita RA, Gomez RS. Treatment of a central giant cell granuloma with intralesional corticosteroid. Br J Oral Maxillofac Surg. 2005;43(1):74–6.

    Article  PubMed  Google Scholar 

  18. Carvalho VM, Perdigao PF, Pimenta FJ, de Souza PE, Gomez RS, De Marco L. A novel mutation of the SH3BP2 gene in an aggressive case of cherubism. Oral Oncol. 2008;44(2):153–5.

    Article  PubMed  CAS  Google Scholar 

  19. Carvalho VM, Perdigao PF, Amaral FR, de Souza PE, De Marco L, Gomez RS. Novel mutations in the SH3BP2 gene associated with sporadic central giant cell lesions and cherubism. Oral Dis. 2009;15(1):106–10.

    Article  PubMed  CAS  Google Scholar 

  20. Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 1993;74(4):609–19.

    Article  PubMed  CAS  Google Scholar 

  21. Pammer J, Weninger W, Hulla H, Mazal P, Horvat R. Expression of regulatory apoptotic proteins in peripheral giant cell granulomas and lesions containing osteoclast-like giant cells. J Oral Pathol Med. 1998;27(6):267–71.

    Article  PubMed  CAS  Google Scholar 

  22. Chuong R, Kaban LB, Kozakewich H, Perez-Atayde A. Central giant cell lesions of the jaws: a clinicopathologic study. J Oral Maxillofac Surg. 1986;44(9):708–13.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported in part by grants from Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) and by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil. Dr. Bernardes VF and RS Gomez are research fellows of CNPq.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Fabrício Rezende Amaral, Vanessa Fátima Bernardes, Alessandra Pires Duarte & Ricardo Santiago Gomez

  2. Department of Pathology, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte, MG, Brazil, CEP 31270 901

    Núbia Braga Pereira, Anilton César Vasconcelos, Ricardo Santiago Gomez & Carolina Cavaliéri Gomes

Authors
  1. Fabrício Rezende Amaral
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vanessa Fátima Bernardes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alessandra Pires Duarte
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Núbia Braga Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anilton César Vasconcelos
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ricardo Santiago Gomez
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Carolina Cavaliéri Gomes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carolina Cavaliéri Gomes.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Amaral, F.R., Bernardes, V.F., Duarte, A.P. et al. Quantitative expression analysis of apoptotic/antiapoptotic genes and association with immunolocalization of BAX and BCL-2 in peripheral and central giant cell lesions of the jaws. Tumor Biol. 32, 997–1003 (2011). https://doi.org/10.1007/s13277-011-0201-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-011-0201-6

Keywords

Search

Navigation