Chano Tokuhiro, Mori Kanji, Scotlandi Katia, Benini Stefania, Lapucci Cristina, Manara Maria Cristina, Serra Massimo, Picci Piero, Okabe Hidetoshi, Baldini Nicola
Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga 520-2192, Japan.
Oncol Rep. 2004 Jun;11(6):1257-63.
Multidrug resistance (MDR) to anticancer agents is a major barrier to the successful treatment of human osteosarcomas. Current understanding of the genes that contribute to the features of MDR is limited, and the mechanisms remain unclear. Here we applied differential display reverse transcription-polymerase chain reaction (DDRT-PCR) to parental and MDR-variants of U-2 OS human osteosarcoma cells, to clarify the genes involved in the MDR cells, and identified five candidate genes. These are BCRP (breast cancer resistance protein) encoding a transmembrane efflux pump; RB1CC1 (RB1-inducible coiled-coil 1), a tumor suppressor regulating RB1 (retinoblastoma 1) expression; a novel transcriptional variant of dUTPase; SSR2 (beta-signal sequence receptor), which is associated with protein translocation across ER membrane; and HSP105 encoding high molecular mass heat shock proteins. Molecular and biological characterization of these genes will yield further insight into the features between MDR and tumor progression in human osteosarcomas.
对抗癌药物的多药耐药性(MDR)是成功治疗人类骨肉瘤的主要障碍。目前对导致MDR特征的基因的了解有限,其机制仍不清楚。在此,我们应用差异显示逆转录-聚合酶链反应(DDRT-PCR)技术,对U-2 OS人骨肉瘤细胞的亲本细胞和MDR变异体进行分析,以阐明参与MDR细胞的基因,并鉴定出五个候选基因。它们分别是编码跨膜外排泵的BCRP(乳腺癌耐药蛋白);调节RB1(视网膜母细胞瘤1)表达的肿瘤抑制因子RB1CC1(RB1诱导的卷曲螺旋1);dUTPase的一种新型转录变体;与蛋白质跨内质网膜转运相关的SSR2(β信号序列受体);以及编码高分子量热休克蛋白的HSP105。对这些基因的分子和生物学特性进行研究,将有助于进一步深入了解人类骨肉瘤中MDR与肿瘤进展之间的关系。