Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Synaptic Vesicle Protein 2 (SV2) Isoforms

  • Bandala, Cindy (Research Support Group, National Institute of Rehabilitation, Escuela Superior de Medicina, Instituto Politecnico Nacional) ;
  • Miliar-Garcia, A. (Oncology and Oxidative Stress Laboratory, Escuela Superior de Medicina, Instituto Politecnico Nacional) ;
  • Mejia-Barradas, C.M. (Research Support Group, National Institute of Rehabilitation, Escuela Superior de Medicina, Instituto Politecnico Nacional) ;
  • Anaya-Ruiz, M. (Molecular Biology Laboratory, Escuela Superior de Medicina, Instituto Politecnico Nacional) ;
  • Luna-Arias, J.P. (Cell Biology Laboratory, Eastern Biomedical Research Center, Instituto Mexicano del Seguro Social) ;
  • Bazan-Mendez, C.I. (Cell Biology Laboratory, Eastern Biomedical Research Center, Instituto Mexicano del Seguro Social) ;
  • Gomez-Lopez, M. (Oncology and Oxidative Stress Laboratory, Escuela Superior de Medicina, Instituto Politecnico Nacional) ;
  • Juarez-Mendez, S. (Cell Biology Laboratory, CINVESTAV) ;
  • Lara-Padilla, E. (Research Support Group, National Institute of Rehabilitation, Escuela Superior de Medicina, Instituto Politecnico Nacional)
  • Published : 2012.10.31
Download PDF
⟨ Previous Next ⟩

Abstract

New molecular markers of cancer had emerged with novel applications in cancer prevention and therapeutics, including for breast cancer of unknown causes, which has a high impact on the health of women worldwide. The purpose of this research was to detemine protein and mRNA expression of synaptic vesicle 2 (SV2) isoforms A, B and C in breast cancer cell lines. Cultured cell lines MDA-MB-231, SKBR3, T47D were lysed and their protein and mRNA expression analyzed by real-time PCR and western blot technique, respectively. SV2A, B proteins were identified in non-tumor (MCF-10A) and tumor cell lines (MDA-MB-231 and T47D) while SV2C only was found in the T47D cell line. Furthermore, the genomic expression was consistent with protein expression for a such cell line, but in MDA-MB-231 there was no SV2B genomic expression, and the SV2C mRNA and protein were not found in the non tumoral cell line. These findings suggest a possible cellular transdifferentiation to neural character in breast cancer, of possible relevance to cancer development, and point to possible use of SV2 as molecular marker and a vehicle for cancer treatment with botulinum toxin.

Keywords

References

  1. Ahnert-Hilger G, Kutay U, Chahoud I, Rapoport T, Wiedenmann B (1996) Synaptobrevin is essential for secretion but not for the development of synaptic processes. Eur J Cell Biol 70, 1-11 https://doi.org/10.1016/S0006-3495(96)79656-X
  2. Arnon SS, Schechter R, Inglesby TV, et al (2001). Botulinum toxin as a biological weapon: medical and public health management. JAMA, 285, 1059-70 https://doi.org/10.1001/jama.285.8.1059
  3. Bajjalieh SM, Frantz GD, Weimann JM, McConnell SK, Scheller RH (1994). Differential expression of synaptic vesicle protein 2 (SV2) isoforms. J Neurosci, 14, 5223-35
  4. Bajjalieh SM, Peterson K, Linial M, Scheller RH (1993). Brain contains two forms of synaptic vesicle protein 2. Proc Natl Acad Sci U S A, 90, 2150-54 https://doi.org/10.1073/pnas.90.6.2150
  5. Blum FC, Chen C, Kroken AR, Barbieri JT (2012). Tetanus toxin and botulinum toxin a utilize unique mechanisms to enter neurons of the central nervous system. Infect Immun 80, 1662-69 https://doi.org/10.1128/IAI.00057-12
  6. Bumming P, Nilsson O, Ahlman H, et al (2007). Gastrointestinal stromal tumors regularly express synaptic vesicle proteins: evidence of a neuroendocrine phenotype. Endocr Relat Cancer 14, 853-63 https://doi.org/10.1677/ERC-06-0014
  7. Coelho A, Dinis P, Pinto R, et al (2010). Distribution of the high-affinity binding site and intracellular target of botulinum toxin type A in the human bladder. Eur Urol 57, 884-90 https://doi.org/10.1016/j.eururo.2009.12.022
  8. Chan DA, Giaccia AJ (2007). Hypoxia, gene expression, and metastasis. Cancer Metastasis Rev, 26, 333-39 https://doi.org/10.1007/s10555-007-9063-1
  9. Chancellor MB, Fowler CJ, Apostolidis A, et al (2008). Drug Insight: biological effects of botulinum toxin A in the lower urinary tract. Nat Clin Pract Urol, 5, 319-28
  10. Choi J, Hwang YK, Choi YJ, et al (2007). Neuronal apoptosis inhibitory protein is overexpressed in patients with unfavorable prognostic factors in breast cancer. J Korean Med Sci, 22, 17-23 https://doi.org/10.3346/jkms.2007.22.S.S17
  11. de Groot M, Aronica E, Heimans JJ, Reijneveld JC (2011). Synaptic vesicle protein 2A predicts response to levetiracetam in patients with glioma. Neurology, 77, 532-39 https://doi.org/10.1212/WNL.0b013e318228c110
  12. de Groot M, Toering ST, Boer K, et al (2010). Expression of synaptic vesicle protein 2A in epilepsy-associated brain tumors and in the peritumoral cortex. Neuro Oncol, 12: 265-73 https://doi.org/10.1093/neuonc/nop028
  13. Dong M, Yeh F, Tepp WH, et al (2006). SV2 is the protein receptor for botulinum neurotoxin A. Science, 312, 592-96 https://doi.org/10.1126/science.1123654
  14. Gillies RJ, Gatenby RA (2007) Hypoxia and adaptive landscapes in the evolution of carcinogenesis. Cancer Metastasis Rev, 26, 311-17 https://doi.org/10.1007/s10555-007-9065-z
  15. Gronberg M, Amini RM, Stridsberg M, Janson ET, Saras J (2010). Neuroendocrine markers are expressed in human mammary glands. Regul Pept, 160, 68-74 https://doi.org/10.1016/j.regpep.2009.12.011
  16. Hanoun N, Bureau C, Diab T, et al (2010). The SV2 variant of KLF6 is down-regulated in hepatocellular carcinoma and displays anti-proliferative and pro-apoptotic functions. J Hepatol 53, 880-88 https://doi.org/10.1016/j.jhep.2010.04.038
  17. Jakobsen AM, Ahlman H, Wangberg B, et al (2002). Expression of synaptic vesicle protein 2 (SV2) in neuroendocrine tumours of the gastrointestinal tract and pancreas. J Pathol, 196, 44-50 https://doi.org/10.1002/path.1002
  18. Janz R, Hofmann K, Sudhof TC (1998). SVOP, an evolutionarily conserved synaptic vesicle protein, suggests novel transport functions of synaptic vesicles. J Neurosci, 18, 9269-81
  19. Janz R, Sudhof TC (1999). SV2C is a synaptic vesicle protein with an unusually restricted localization: anatomy of a synaptic vesicle protein family. Neuroscience, 94, 1279-90 https://doi.org/10.1016/S0306-4522(99)00370-X
  20. Karsenty G, Rocha J, Chevalier S, et al (2009). Botulinum toxin type A inhibits the growth of LNCaP human prostate cancer cells in vitro and in vivo. Prostate, 69, 1143-50 https://doi.org/10.1002/pros.20958
  21. Li Q, Johansson H, Grimelius L (1999). Innervation of human adrenal gland and adrenal cortical lesions. Virchows Arch, 435, 580-89 https://doi.org/10.1007/s004280050444
  22. Lukashev D, Ohta A, Sitkovsky M (2007). Hypoxia-dependent anti-inflammatory pathways in protection of cancerous tissues. Cancer Metastasis Rev, 26, 273-79 https://doi.org/10.1007/s10555-007-9054-2
  23. McPherson K, Steel CM, Dixon JM (2000). ABC of breast diseases. Breast cancer-epidemiology, risk factors, and genetics. BMJ 321, 624-28 https://doi.org/10.1136/bmj.321.7261.624
  24. Montal M (2010). Botulinum neurotoxin: a marvel of protein design. Annu Rev Biochem, 79, 591-617 https://doi.org/10.1146/annurev.biochem.051908.125345
  25. Nilsson O, Jakobsen AM, Kolby L, Bernhardt P, Forssell- Aronsson E, Ahlman H (2004). Importance of vesicle proteins in the diagnosis and treatment of neuroendocrine tumors. Ann N Y Acad Sci, 1014, 280-83 https://doi.org/10.1196/annals.1294.032
  26. Portela-Gomes GM, Lukinius A, Grimelius L (2000). Synaptic vesicle protein 2, A new neuroendocrine cell marker. Am J Pathol, 157, 1299-1309 https://doi.org/10.1016/S0002-9440(10)64645-7
  27. Schiavo G, Matteoli M, Montecucco C (2000). Neurotoxins affecting neuroexocytosis. Physiol Rev, 80, 717-66
  28. Shi J, Anderson D, Lynch BA, et al (2011). Combining modelling and mutagenesis studies of synaptic vesicle protein 2A to identify a series of residues involved in racetam binding. Biochem Soc Trans, 39, 1341-47 https://doi.org/10.1042/BST0391341
  29. Simpson LL (1979). Studies on the mechanism of action of botulinum toxin. Adv Cytopharmacol, 3, 27-34
  30. Zhang Q, Fan H, Shen J, Hoffman RM, Xing HR (2010). Human breast cancer cell lines co-express neuronal, epithelial, and melanocytic differentiation markers in vitro and in vivo. PLoS One, 5,9712 https://doi.org/10.1371/journal.pone.0009712
  31. Zhenzhen Z, De'an T, Limin X, Wei Y, Min L (2012). New Candidate Tumor-Suppressor Gene KLF6 and its Splice Variant KLF6 SV2 Counterbalancing Expression in Primary Hepatocarcinoma. Hepatogastroenterology, 59, 473-76

Cited by

  1. Neural Transdifferentiation: MAPTau Gene Expression in Breast Cancer Cells vol.17, pp.4, 2016, https://doi.org/10.7314/APJCP.2016.17.4.1967