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Basic Sciences

Expression of a Human Multidrug Resistance Gene in Ovarian Carcinomas

Jean Bourhis, Lori J. Goldstein, Guy Riou, Ira Pastan, Michael M. Gottesman and Jean Bénard
Jean Bourhis
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Lori J. Goldstein
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Guy Riou
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Ira Pastan
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Michael M. Gottesman
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Jean Bénard
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DOI:  Published September 1989
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Abstract

Expression of the human MDR1 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 MDR1 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 MDR1 complementary DNA and human γ-actin complementary DNA probes sequentially as qualitative and quantitative controls. MDR1 transcripts (4.5 kilobases) were observed 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 cis-platinum, no transcript could be detected. Using the exact Fisher test, the difference between the 2 groups was found to be significant (P < 0.01). The three tumors with elevated MDR1 expression did not show MDR1 DNA amplification. Our study suggests that, in spite of the weak occurrence of the MDR process in patients with ovarian cancers, MDR1 expression can be related to previous treatment with doxorubicin or vincristine. These results favor the expression of the MDR1 gene as one of the determinants involved in the acquired chemoresistance of ovarian cancers.

Footnotes

  • ↵1 This work was supported by Association pour la Recherche sur le Cancer (Villejuif, France) and Institut Gustave Roussy (Contrat de Recherche Clinique N. 88 D20).

  • ↵2 To whom requests for reprints should be addressed.

  • Received January 18, 1989.
  • Revision received June 7, 1989.
  • Accepted June 16, 1989.
  • ©1989 American Association for Cancer Research.
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September 1989
Volume 49, Issue 18
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Expression of a Human Multidrug Resistance Gene in Ovarian Carcinomas
Jean Bourhis, Lori J. Goldstein, Guy Riou, Ira Pastan, Michael M. Gottesman and Jean Bénard
Cancer Res September 15 1989 (49) (18) 5062-5065;

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Expression of a Human Multidrug Resistance Gene in Ovarian Carcinomas
Jean Bourhis, Lori J. Goldstein, Guy Riou, Ira Pastan, Michael M. Gottesman and Jean Bénard
Cancer Res September 15 1989 (49) (18) 5062-5065;
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