Expression of the cisplatin resistance phenotype in a human ovarian carcinoma cell line segregates with chromosomes 11 and 16.
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.
Mirakhur
B
B
Department of Pathology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Parekh
H K
HK
Simpkins
H
H
D000818:Animals; D002277:Carcinoma / Q000473:pathology*; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005799:Genes, Dominant; D006801:Humans; D006822:Hybrid Cells; D007739:L Cells; D051379:Mice; D010051:Ovarian Neoplasms / Q000473:pathology*; D010641:Phenotype; D014407:Tumor Cells, Cultured / Q000187:drug effects
D002945:Cisplatin