Association of copper transporter expression with platinum resistance in epithelial ovarian cancer.

Copper transporters (CTR) also regulate the cellular transport of platinum drugs, but their role in platinum resistance of ovarian cancer has not been elucidated. CTR expression in ovarian cancer tissues resected from patients treated by platinum-based chemotherapy was evaluated immunohistochemically. CTR2 expression in ovarian cancer cells was inhibited by bathocuproine disulfonate, and the changes in cisplatin sensitivity were examined. CTR2 expression was increased in chemoresistant patients, but not significantly. However, the CTR2/CTR1 ratio was significantly increased in chemoresistant patients. Cases with positive CTR2 expression or positive CTR2/CTR1 ratio had poor prognoses. When the CTR2 expression in ovarian cancer cells was suppressed, sensitivity to cisplatin was significantly increased. These data suggest that CTR2 contributes to platinum resistance in ovarian cancer. The CTR2/CTR1 ratio is a useful marker for platinum sensitivity and a potential prognostic factor in patients with ovarian cancer.