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

Author(s):Show less -

Valera, Elvis Terci ^[1] ; Abdalla de Freitas Cortez, Maria Angelica ^[1] ; de Paula Queiroz, Rosane Gomes ^[1] ; de Oliveira, Fabio Morato ^[1] ; Brassesco, Maria Sol ^[2] ; Jabado, Nada ^[3] ; Faury, Damien ^[3] ; Bobola, Michael S. ^{[4, 5]} ; Machado, Helio Rubens ^[6] ; Scrideli, Carlos Alberto ^[1] ; Tone, Luiz Gonzaga ^[1]

Affiliation

^[1] Univ Sao Paulo, Div Pediat Oncol, Dept Pediat, Fac Med Ribeirao Preto, BR-14048900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Genet, Fac Med Ribeirao Preto, BR-14048900 Sao Paulo - Brazil

^[3] McGill Univ, Dept Pediat, Div Hemtooncol, Montreal, PQ H3A 2T5 - Canada

^[4] Childrens Hosp, Div Pediat Oncol, Seattle, WA - USA

^[5] Reg Med Ctr, Seattle, WA - USA

^[6] Univ Sao Paulo, Div Neurosurg, Dept Surg & Anat, Fac Med Ribeirao Preto, BR-14048900 Sao Paulo - Brazil

• Document type: Journal article
• Source: CHILD'S NERVOUS SYSTEM; v. 25, n. 1, p. 39-45, JAN 2009.
• Web of Science Citations: 13

Abstract

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. 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. 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. 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. 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. (AU)