Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) as a chemoresistance marker in human solid carcinomas.

The incidence and mortality of human solid carcinoma has not declined in the past decade. This is due to the lack of new effective therapy. The treatment with anticancer drug-based chemotherapy after reductive surgery has improved the prognosis of patients with several types of human solid carcinomas, however the complete pathologic response and 5-year survival rates have not improved. One of the most important problems in the treatment of human solid carcinoma is the intrinsic/acquired resistance to anticancer drug-based chemotherapy. Knowledge of the active mechanism of drug resistance may lead to new treatment strategies and allows the selection of those patients for specific treatment modalities. Cisplatin is one of the active anticancer drug, widely used in clinic. Multidrug resistance (MDR) has been noted as an important mechanism of drug resistance. Several genes including MDR1, MRP and LRP have been identified. MDR1 and MRP1 function as a drug efflux pump and are classified as ABC transporter gene family, and are expressed in both human solid tumors and hematological malignancies. The 110-kd LRP, the major vault protein, is frequently overexpressed in MDR cells, and has an important role(s) in transport of drugs from nuclei to cytoplasm and confers to MDR in vitro. Recently, BCRP (MXR/ABCP) gene, another member of the ABC transporter family, has been described in breast, colon, gastric and fibrosarcoma cell lines. However, no evidence(s) that these molecules are involved in cisplatin resistance in vitro and in clinic, has been reported. ThereExpression of Copper-transporting P-type Adenosine Triphosphatase (ATP7B) as a Chemoresistance Marker in Human Solid Carcinomas