Copper mixed up in cisplatin resistance

Cisplatin is an effective anti cancer drug but some tumors are resistant to treatment with this compound. However, the molecular mechanisms involved in cisplatin resistance have been poorly understood. In the September 30 Early Edition of the Proceedings of the National Academy of Sciences of the USA, Seiko Ishida and colleagues at the University of California, San Francisco, US, show the copper transporter Ctr1 in yeast and mammals mediates that uptake of the cisplatin (PNAS, DOI/10.1073.162491399, September 30, 2002).

Ishida et al. observed that deletion of the yeast CTR1 gene —encoding a high-affinity copper transporter — resulted in increased cisplatin resistance and reduced intracellular accumulation of cisplatin. Cisplatin also caused degradation and delocalization of Ctr1p and interfered with copper uptake in wild-type yeast cells. In addition, they showed that mouse cell lines lacking one or both mouse Ctr1 (mCtr1) alleles had increased cisplatin resistance and decreased cisplatin accumulation in parallel ...