Pediatric glioblastoma cell line shows different patterns of expression of transmembrane ABC transporters after in vitro exposure to vinblastine |
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Authors: | Elvis Terci Valera Maria Angélica Abdalla de Freitas Cortez Rosane Gomes de Paula Queiroz Fabio Morato de Oliveira María Sol Brassesco Nada Jabado Damien Faury Michael S Bobola Hélio Rubens Machado Carlos Alberto Scrideli Luiz Gonzaga Tone |
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Institution: | 1. Division of Pediatric Oncology, Department of Pediatrics, Faculty of Medicine of Ribeir?o Preto, University of S?o Paulo, 7 andar. Av. Bandeirantes, 3900. Bairro Monte Alegre, CEP 14048-900, Ribeir?o Preto, S?o Paulo, Brazil 2. Department of Genetics, Faculty of Medicine of Ribeir?o Preto, University of S?o Paulo, Ribeir?o Preto, S?o Paulo, Brazil 3. Division of Hemato-Oncology, Department of Pediatrics, Mc Gill University, Montréal, Canada 4. Division of Pediatric Oncology, Children’s Hospital and Regional Medical Center, Seattle, WA, USA 5. Division of Neurosurgery, Department of Surgery and Anatomy, Faculty of Medicine of Ribeir?o Preto, University of S?o Paulo, Ribeir?o Preto, S?o Paulo, Brazil
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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.
Financial support: FAPESP (grant 2007/04065-9). |
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Keywords: | Cancer Children Brain tumor Cell lines Drug resistance Chemotherapy Genetics |
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