[Expression of P-glycoprotein 170 (GP 170) and drug resistance in human cancers]

Abstract

In vitro models with multiple drug resistance (MDR) phenotype have been frequently related to hyperproduction of the 170 kd membrane glycoprotein, the so-called 170 GP. This protein is a pump able to extrude from cytoplasm drugs with various structures and mechanisms such as doxorubicin (DXR) or vinblastin (VLB). The MDR1 gene encodes the GP 170. MDR1 gene expression is low in most of the normal tissues, but high in some tissues such as colon, kidney, or liver. In these tissues, the GP 170 would ensure a detoxifying function related to cellular toxic compounds. There is a broad range of MDR1 gene expression in human tumors as a result of several factors. Of particular importance are the tissue origin from which the cancer derives and previous chemotherapy. In some cancers which often exhibit acquired chemoresistance, such as non Hodgkin's lymphomas, leukemias, sarcomas or neuroblastomas, an increase of MDR1 gene expression following previous chemotherapy has been frequently observed. Moreover in these cancers, a relationship between MDR1 transcript levels and clinical response to chemotherapy could exist as shown in several studies including one of ours. Hematosarcoma in the adult and some pediatric cancers seem to be models in which MDR1 gene expression may have a clinical relevance. Thus, an increase of MDR1 gene expression during the course of chemotherapy would lead the clinician to choose "non MDR related" agents such as DXR, VLB; or to use agents that are able to reverse MDR phenotype.