Expression of a Human Multidrug Resistance Gene in Ovarian

Expression of the human MDR\ gene has been shown to confer the multidrug resistance (MDR) phenotype to sensitive cells. To investigate the possible contribution of the MDR phenotype to chemoresistance in ovarian carcinoma, we have analyzed MDR\ gene expression in fresh carcinoma specimens from 50 patients. Fifteen received chemotherapy before surgery and were judged as poor responders. Thirty-five patients did not receive any drug before surgery. Control tissues were lymphocytes from 7 patients. Total RNAs were analyzed by Northern and slot blot hybridization techniques using human MDR\ complementary DNA and human -y-actin complementary DNA probes sequentially as qualitative and quantitative controls. MDRl transcripts (4.5 kilobases) were ob served in the RNA preparations obtained from 3 of 10 patients who were treated with doxorubicin or vincristine, 2 drugs known to select the MDR phenotype in vitro. In 40 other RNA preparations obtained from 35 untreated patients and 5 patients treated exclusively with cyclophosphamide and en-platinum, no transcript could be detected. Using the exact Fisher test, the difference between the 2 groups was found to be significant (/' < 0.01). The three tumors with elevated MDR\ expression did not show MDR\ DNA amplification. Our study suggests that, in spite of the weak occurrence of the MDR process in patients with ovarian cancers, MDRl expression can be related to previous treatment with doxorubicin or vincristine. These results favor the expression of the MDRl gene as one of the determinants involved in the acquired chemoresistance of ovarian cancers.