The response of Saccharomyces cerevisiae to cisplatin was investigated by 
examining variations in gene expression using cDNA microarrays and confirming 
the results by reverse transcription polymerase chain reaction (RT-PCR). The 
mRNA levels of 14 proteins involved in iron homeostasis were shown to be 
increased by cisplatin. Interestingly, the expression of all 14 genes is known 
to be regulated by Aft1, a transcription factor activated in response to iron 
insufficiency. The promoter of one of these genes, FET3, has been relatively 
well studied, so we performed a reporter assay using the FET3 promoter and 
showed that an Aft1 binding site in the promoter region is indispensable for 
induction of transcription by cisplatin. The active domain of Aft1 necessary for 
activation of the FET3 promoter by cisplatin is identical to the one required 
for activation by bathophenanthroline sulfonate, an inhibitor of cellular iron 
uptake. Furthermore, we found that cisplatin inhibits the uptake of (55)Fe(II) 
into yeast cells. These findings suggest that cisplatin activates Aft1 through 
the inhibition of iron uptake into the cells, after which the expression of Aft1 
target genes involved in iron uptake might be induced.