Sorcin, an important gene associated with multidrug-resistance in human leukemia cells

Sorcin, or soluble resistance-related calcium-binding protein, is a 22 kD calcium-binding protein initially identified in many mutlidrug resistant (MDR) cell lines. We previously observed by gene profiling that sorcin is significantly up-regulated in a doxorubicin-induced MDR leukemia cell line, K562/A02, over its parent cells. We have also demonstrated that the level of sorcin expression in leukemia patients correlates not only directly with that of the mdr1 gene, but also inversely with patients’ response to chemotherapies and overall prognosis. In this report, we have carried out experiments to dissect out the contribution of sorcin by itself to drug resistant phenotype in K562 cells. Overexpression of sorcin protein by gene transfection in K562 cells resulted in increased drug resistance, from 4.1- to 22.5-fold, to a variety of chemotherapeutic agents, including doxorubicin, etoposide, homoharringtonine and vincristine. On the other hand, inhibition of sorcin expression in both MDR K562/A02 and the sorcin-transfected K562 cells with sorcin-targeting small interfering RNA led to varying exten