Role of Transporter Genes in Cisplatin Resistance

Abstract

The 50% inhibitory concentration (IC₅₀) values for cisplatin from 60 cell lines of the National Cancer Institute (NCI), USA, were correlated with the microarray-based mRNA expression levels of 55 transporter genes. The transporters are known to be involved in multiple drug resistance and belong to different classes, e.g. lysosomal H⁺ transporting ATPases, Cu²⁺ transporting ATPases, glutamate transporters of the solute carrier family 31, copper transporters of the solute carrier family 31, and ATP-binding cassette (ABC) transporter genes. The expression levels of 17 genes represented by 21 clones correlated significantly with the IC₅₀ values for cisplatin. Hierarchical cluster analysis further enabled the prediction of the sensitivity or resistance of these cell lines to cisplatin with respect to the mRNA expression of these set of transporter genes under study. One among the 17 genes studied is ATP7B which is involved in the transport of copper ions across the cell membrane into the cell. We conclude that our microarray-based approach is a feasible and effective tool in identifying prognostic markers for drug resistance in antitumor therapy.