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Pediatric glioblastoma cell line shows different patterns of expression of transmembrane ABC transporters after in vitro exposure to vinblastine

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Abstract

Background

Resistance to drug is a major cause of treatment failure in pediatric brain cancer. The multidrug resistance (MDR) phenotype can be mediated by the superfamily of adenosine triphosphate-binding cassette (ABC) transporters. The dynamics of expression of the MDR genes after exposure to chemotherapy, especially the comparison between pediatric brain tumors of different histology, is poorly described.

Objective

To compare the expression profiles of the multidrug resistance genes ABCB1, ABCC1, and ABCG2 in different neuroepithelial pediatric brain tumor cell lines prior and following short-term culture with vinblastine.

Methods

Immortalized lineages from pilocytic astrocytoma (R286), anaplasic astrocytoma (UW467), glioblastoma (SF188), and medulloblastoma (UW3) were exposed to vinblastine sulphate at different schedules (10 and 60 nM for 24 and 72 h). Relative amounts of mRNA expression were analyzed by real-time quantitative polymerase chain reaction. Protein expression was assessed by immunohistochemistry for ABCB1, ABCC1, and ABCG2.

Results

mRNA expression of ABCB1 increased together with augmenting concentration and time of exposure to vinblastine for R286, UW467, and UW3 cell lines. Interestingly, ABCB1 levels of expression diminished in SF188. Following chemotherapy, mRNA expression of ABCC1 decreased in all cell lines other than glioblastoma. ABCG2 expression was influenced by vinblastine only for UW3. The mRNA levels showed consistent association to protein expression in the selected sets of cell lines analyzed.

Conclusions

The pediatric glioblastoma cell line SF188 shows different pattern of expression of multidrug resistance genes when exposed to vinblastine. These preliminary findings may be useful in determining novel strategies of treatment for neuroepithelial pediatric brain tumors.

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Acknowledgements

The authors thank the Fundação de Amparo a Pesquisa do Estado de São Paulo—FAPESP—for the financial support on this research (proc.: 2007/04065-9). The authors also thank Dr. Daniel Ferracioli Brandão for his assistance in the IH assays and the Clinical Hospital of Ribeirão Preto—in special Andrea Queiroz Ungari; PhC and Joneval Borges de Ledo Junior; PhC, from the Chemoterapy Unit—for kindly provide us with the aliquotes of vinblastine sulphate.

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Authors and Affiliations

  1. Division of Pediatric Oncology, Department of Pediatrics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 7 andar. Av. Bandeirantes, 3900. Bairro Monte Alegre, CEP 14048-900, Ribeirão Preto, São Paulo, Brazil

    Elvis Terci Valera, Maria Angélica Abdalla de Freitas Cortez, Rosane Gomes de Paula Queiroz, Fabio Morato de Oliveira, Carlos Alberto Scrideli & Luiz Gonzaga Tone

  2. Department of Genetics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    María Sol Brassesco

  3. Division of Hemato-Oncology, Department of Pediatrics, Mc Gill University, Montréal, Canada

    Nada Jabado & Damien Faury

  4. Division of Pediatric Oncology, Children’s Hospital and Regional Medical Center, Seattle, WA, USA

    Michael S. Bobola

  5. Division of Neurosurgery, Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Hélio Rubens Machado

Authors
  1. Elvis Terci Valera
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  2. Maria Angélica Abdalla de Freitas Cortez
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  3. Rosane Gomes de Paula Queiroz
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  4. Fabio Morato de Oliveira
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  8. Michael S. Bobola
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  9. Hélio Rubens Machado
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  10. Carlos Alberto Scrideli
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  11. Luiz Gonzaga Tone
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Corresponding author

Correspondence to Elvis Terci Valera.

Additional information

Financial support: FAPESP (grant 2007/04065-9).

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Valera, E.T., Cortez, M.A.A.d.F., Queiroz, R.G.d.P. et al. Pediatric glioblastoma cell line shows different patterns of expression of transmembrane ABC transporters after in vitro exposure to vinblastine. Childs Nerv Syst 25, 39–45 (2009). https://doi.org/10.1007/s00381-008-0740-3

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  • DOI: https://doi.org/10.1007/s00381-008-0740-3

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