Subscribe to RSS
DOI: 10.1590/0004-282X20170027
High expression of anti-apoptotic genes in grade I and II meningiomas
Alta expressão de genes anti-apoptóticos em meningiomas graus I e IIABSTRACT
One of the different genetic mechanisms involved in the carcinogenesis of meningiomas is influenced by interactions between proteins that induce and inhibit apoptosis.
Objective
To evaluate the expression of c-FLIP, XIAP, Bcl-2, caspase 3, 8 and 9, cytochrome c, APAF 1 and Smac/DIABLO genes related to apoptosis pathways.
Methods
The gene expression was evaluated in 30 meningiomas (WHO grades I and II) and in 10 normal samples (from arachnoid tissue) through PCR-RT.
Results
The results showed higher expression of anti-apoptotic genes in meningiomas when compared to the control group, which had a low expression of pro-apoptotic genes.
Conclusion
There is a possible block in the activation of caspases through the intrinsic apoptosis pathway in meningiomas. c-FLIP modulates caspase 8 and, by inhibiting its activation due to the lack of connection with the receiver, there is a block to the FAS activation of apoptosis by its extrinsic pathway.
RESUMO
Um dos diferentes mecanismos genéticos envolvidos na carcinogênese de meningiomas é influenciado por interações entre proteínas que induzem e inibem a apoptose.
Objetivos
Avaliar a expressão de c-FLIP, XIAP, Bcl-2, caspase 3, 8 e 9, citocromo C, APAF 1 e Smac/DIABLO, genes relacionados com as vias da apoptose.
Métodos
A expressão gênica foi avaliada em trinta amostras de meningiomas (OMS grau I e II) e em dez amostras normais (de aracnóide) por PCR em tempo real.
Resultados
Os resultados mostraram maior expressão de genes antiapoptóticos em meningiomas quando comparados com controle, em contraste com a menor expressão de genes próapoptóticos.
Conclusão
Há um possível bloqueio na ativação de caspases através da via intrínseca da apoptose em meningiomas. O c-FLIP modula a caspase 8 e, desse modo, inibindo a sua ativação pela ausência de ligação com o receptor, há um bloqueio na ativação de FAS pela via extrínseca da apoptose.
Publication History
Received: 14 September 2016
Accepted: 27 December 2016
Article published online:
05 September 2023
© 2023. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil
-
References
- 1 Wiemels J, Wrensch M, Claus EB. Epidemiology and etiology of meningioma. J Neurooncol. 2010;99(3):307-14. https://doi.org/10.1007/s11060-010-0386-3
- 2 Al-Mefty O, Kadri PA, Pravdenkova S, Sawyer JR, Stangeby C, Husain M. Malignant progression in meningioma: documentation of a series and analysis of cytogenetic findings. J Neurosurg. 2004;101(2):210-8. https://doi.org/10.3171/jns.2004.101.2.0210
- 3 Perry A, Gutmann DH, Reifenberger G. Molecular pathogenesis of meningiomas. J Neurooncol. 2004;70(2):183-202. https://doi.org/10.1007/s11060-004-2749-0
- 4 Whittle IR, Smith C, Navoo P, Collie D. Meningiomas. Lancet. 2004;363(9420):1535-43. https://doi.org/10.1016/S0140-6736(04)16153-9
- 5 Boldrini L, Pistolesi S, Gisfredi S, Ursino S, Ali G, Pieracci N et al. Expression of endothelin 1 and its angiogenic role in meningiomas. Virchows Arch. 2006;449(5):546-53. https://doi.org/10.1007/s00428-006-0273-7
- 6 Alexiou GA, Gogou P, Markoula S, Kyrutsus AP. Management of meningiomas. Clin Neurol Neurosurg. 2010;112(3):177-82. http://doi.org/10.1016/j.clineuro.2009.12.011
- 7 Koschny R, Krupp W, Xu Li-Xin, Mueller WC, Bauer M, Sinn P et al. WHO grade related expression of TRAIL-receptors and apoptosis regulators in meningioma. Pathol Res Pract. 2015;211(2):109-16. http://doi.org/10.1016/j.prp.2014.11.002
- 8 Takahashi JA, Ueba T, Hashimoto N, Nakashima Y, Katsuki N. The combination of mitotic and Ki-67 indices as a useful method for predicting short-term recurrence of meningiomas. Surg Neurol. 2004;61(2):149-55. https://doi.org/10.1016/S0090-3019(03)00575-5
- 9 Brastianos PK, Horowitz PM, Santagata S, Jones RT, McKenna A, Getz G et al. Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations. Nat Genet. 2013;45(3):285-9. https://doi.org/10.1038/ng.2526
- 10 Kumar S. Mechanisms mediating caspase activation in cell death. Cell Death Differ. 1999;6(11):1060-6. https://doi.org/10.1038/sj.cdd.4400600
- 11 Riedl SJ, Shi Y. Molecular mechanisms of caspase regulation during apoptosis. Nat Rev Mol Cell Biol. 2004;5(11):897-907. https://doi.org/10.1038/nrm1496
- 12 Huang Y, Park YC, Rich RL, Segal D, Myszka DG, Wu H. Structural basis of caspase inhibition by XIAP: differential roles of the linker versus the BIR domain. Cell. 2001;104(5):781-90. http://dx.doi.org/10.1016/S0092-8674(01)00273-2
- 13 Siegelin MD, Kossatz LS, Winckler J, Rami A. Regulation of XIAP and Smac/DIABLO in the rat hippocampus following transient forebrain ischemia. Neurochem Int. 2005;46(1):41-51. https://doi.org/10.1016/j.neuint.2004.07.009
- 14 Creagh EM, Murphy BM, Duriez PJ, Duckett CS, Martin SJ. Smac/Diablo antagonizes ubiquitin ligase activity of inhibitor of apoptosis proteins. J Biol Chem. 2004;279(26):26906-14. https://doi.org/10.1074/jbc.M313859200
- 15 Wu G, Chai J, Suber TL, Wu JW, Du C, Wang X et al. Structural basis of IAP recognition by Smac/DIABLO. Nature. 2000;408(6815):1008-12. https://doi.org/10.1038/35050012
- 16 Louis DN, Perry A, Reifenberger G, Deimling A, Figarella-Branger D, Cavenee WK et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016;131(6):803-20. https://doi.org/10.1007/s00401-016-1545-1
- 17 Takei H, Buckleair LW, Powell SZ. Immunohistochemical expression of apoptosis regulating proteins and sex hormone receptors in meningiomas. Neuropathology. 2008;28(1):62-8. https://doi.org/10.1111/j.1440-1789.2007.00852.x
- 18 Konstantinidou AE, Givalos N, Gakiopoulou H, Korkolopoulou P, Kotsiakis X, Boviatsis E et al. Caspase-3 immunohistochemical expression is a marker of apoptosis, increased grade and early recurrence in intracranial meningiomas. Apoptosis. 2007;12(4):695-705. https://doi.org/10.1007/s10495-006-0001-4
- 19 Konstantinidou AE, Pavlopoulos PM, Patsouris E, Kaklamanis L, Davaris P. Expression of apoptotic and proliferation markers in meningiomas. J Pathol. 1998;186(3):325-30. https://doi.org/10.1002/(SICI)1096-9896(1998110)186:3<325::AID-PATH168>3.0.CO;2-U
- 20 Verheijen FM, Donker GH, Viera CS, Sprong M, Jacobs HM, Blaauw G et al. Progesterone receptor, bc1-2 and bax expression in meningiomas. J Neurooncol. 2002;56(1):35-41. https://doi.org/10.1023/A:1014404918118
- 21 Karamitopoulou E, Perentes E, Tolnay M, Probst A. Prognostic significance of MIB-1, p53, and bcl-2 immunoreactivity in meningiomas. Hum Pathol. 1998;29(2):140-5.
- 22 Gogineni VR, Gupta R, Nalla AK, Velpula KK, Rao JS. uPAR and cathepsin B shRNA impedes TGF-β1-driven proliferation and invasion of meningioma cells in a XIAP-dependent pathway. Cell Death Dis. 2012;3(12):E439. https://doi.org/10.1038/cddis.2012.170
- 23 Rajaraman P, Wang SS, Rothman N, Brown MM, Black PM, Fine HA et al. Polymorphisms in apoptosis and cell cycle control genes and risk of brain tumors in adults. Cancer Epidemiol Biomarkers Prev. 2007;16(8):1655-61. https://doi.org/10.1158/1055-9965.EPI-07-0314
- 24 Salvesen GS, Duckett CS. IAP proteins: blocking the road to death’s door. Nat Re Mol Cell Biol. 2002;3(6):401-10. https://doi.org/10.1038/nrm830
- 25 Jönsson G, Paulie S, Grandien A. High level of cFLIP correlates with resistance to death receptor-induced apoptosis in bladder carcinoma cells. Anticancer Res. 2003;23(2B):1213-8.
- 26 Koschny R, Walczak H, Ganten TM. The promise of TRAIL: potential and risksvof a novel anticancer therapy. J Mol Med. 2007;85(9):923-35. https://doi.org/10.1007/s00109-007-0194-1
- 27 Marsters SA, Pitti RM, Donahue CJ, Ruppert S, Bauer KD, Ashkenazi A. Activation of apoptosis by Apo-2 ligand is independent of FADD but blocked by CrmA. Curr Biol. 1996;6(6):750-2. https://doi.org/10.1016/S0960-9822(09)00456-4
- 28 Bodmer JL, Holler N, Reynard S, Vinciguerra P, Schneider P, Juo P et al. Trail receptor-2 signals apoptosis through FADD and caspase-8. Nat Cell Biol. 2000;2(4):241-3. https://doi.org/10.1038/35008667
- 29 Irmler M, Thome M, Hahne M, Schneider P, Hofmann K, Steiner V et al. Inhibition of death receptor signals by cellular FLIP. Nature. 1997;388(6638):190-5. https://doi.org/10.1038/40657
- 30 Hao C, Beguinot F, Condorelli G, Trencia A, Van Meir EG, Yong VW et al. Induction and intracellular regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediated apotosis in human malignant glioma cells. Cancer Res. 2001;61(3):1162-70.
- 31 Schneider P, Holler N, Bodmer JL, Hahne M, Frei K, Fontana A et al. Conversion of membrane-bound Fas(CD95) ligand to its soluble form is associated with downregulation of its proapoptotic activity and loss of liver toxicity. J Exp Med 1998;187(8):1205-13. https://doi.org/10.1084/jem.187.8.1205