Mitoxantrone resistance in a small cell lung cancer cell line is associated with ABCA2 upregulation

作者: R Boonstra , H Timmer-Bosscha , J van Echten-Arends , D M van der Kolk , A van den Berg

DOI: 10.1038/SJ.BJC.6601863

关键词: BiologyMitoxantroneABCB5MTT assayMolecular biologyPathologyABCC10EstramustineABCC4Downregulation and upregulationGene expression

摘要: The aim of this study was to find factors that could explain the accumulation difference mitoxantrone in BCRP1-negative GLC4-MITO cell line compared GLC4. Comparative genomic hybridisation (CGH) applied determine chromosomal differences between GLC4 and GLC4-MITO. analysis revealed gain 2q, 6p, 9q, 13q, 14q, 15q, 19q Xp loss 1p, 3p, 3q, 4q, 6q, 8q, 11p, 16p, 17q, 18p, 20p Xq. In over-represented areas, seven transporter genes were identified: ABCB6, ABCB2 (TAP1), ABCB3 (TAP2), ABCF1 (ABC50), ABCC10 (MRP7), ABCA2 (ABC2) ABCC4 (MRP4). No RNA or protein upregulation observed for ABCF1, ABCC10, ABCC4, ABCB3, but an increased expression detected mRNA is known be involved resistance estramustine. MTT assay, two-fold resistant estramustine Coincubation with GLC4-MITO, while not affected This suggests able block efflux cells. These data reveal cellular reduction a mitoxantrone-resistant associated overexpression ABCA2.

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