Mirakhur B, Parekh H K, Simpkins H
Department of Pathology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Cancer Res. 1996 May 15;56(10):2256-62.
Many mechanisms have been proposed to explain cisplatin resistance, suggesting that this phenomenon is multifactorial. In an attempt to define the chromosome(s) responsible for cisplatin resistance in the human ovarian carcinoma 2008/C13* cell lines, somatic cell hybrids were obtained following fusion of the cisplatin-resistant 2008/C13* cells with an A9 rodent fibroblast cell line. The hybrids were then analyzed for segregation of the human chromosomes with the drug-resistant phenotype. Chromosomes 11 and 16 were present in all of the resistant somatic cell hybrids, with the highest concordance for chromosome 16. The role of both of these chromosomes was further established with microcell hybrids. Microcell hybrids of A9 cells with chromosome 16 from the 2008/C13* cells did not exhibit cisplatin resistance, but the presence of a normal chromosome 11 with chromosome 16 (derived from cisplatin-resistant 2008/C13* cells and not from the cisplatin-sensitive 2008 cells) resulted in increased resistance to cisplatin. In addition, loss of chromosome 11 from a resistant somatic cell hybrid resulted in the hybrid becoming sensitive to cisplatin, implicating this chromosome in maintaining the resistant phenotype. The results demonstrate that resistance to cisplatin is a dominant trait in the 2008/C13* human ovarian cells, and both chromosomes 11 and 16 are required for its expression.
人们提出了许多机制来解释顺铂耐药性，这表明这种现象是多因素的。为了确定在人卵巢癌2008/C13细胞系中负责顺铂耐药性的染色体，将顺铂耐药的2008/C13细胞与A9啮齿动物成纤维细胞系融合，获得了体细胞杂种。然后分析这些杂种中人类染色体与耐药表型的分离情况。11号和16号染色体存在于所有耐药体细胞杂种中，其中16号染色体的一致性最高。通过微细胞杂种进一步确定了这两条染色体的作用。A9细胞与来自2008/C13细胞的16号染色体的微细胞杂种没有表现出顺铂耐药性，但正常的11号染色体与16号染色体（来自顺铂耐药的2008/C13细胞而非顺铂敏感的2008细胞）的存在导致对顺铂的耐药性增加。此外，耐药体细胞杂种中11号染色体的缺失导致该杂种对顺铂敏感，这表明该染色体在维持耐药表型中起作用。结果表明，对顺铂的耐药性在2008/C13*人卵巢细胞中是一种显性性状，11号和16号染色体的表达均是其必需的。
