© 1989 by Oxford University Press
Journal of the National Cancer Institute, Vol. 81, No. 2, 116-124,
January 18, 1989
© 1989 Oxford University Press
Expression of Multidrug Resistance Gene in Human Cancers
1(Laboratory of Molecular Biology, Division of Cancer Biology and Diagnosis)
2Second Medical Clinic Garnisongasse 13, A-1090 Vienna, Austria
3Department of Hematology-Oncology, St. Jude Children's Research Hospital, and Department of Pediatrics, University of Tennessee Memphis, TN
4Department of Pediatrics, Washington University School of Medicine St. Louis, MO
5Mayo Clinic Rochester, MN
6(NCI-Navy Medical Oncology Branch, Division of Cancer Treatment)
7(Laboratory of Pathology, Division of Cancer Biology and Diagnosis), National Cancer Institute Bethesda, MD
*Correspondence to: Dr. Michael M. Gottesman, Bldg 37, Rm 2E18, National Institutes of Health, Bethesda, MD 20892
Many cancers have been cured by chemotherapeutic agents. However, other cancers are intrinsically drug resistant, and some acquire resistance following chemotherapy. Cloning of the cDNA for the human MDR1 gene (also known as PGY1), which encodes the multidmg efflux protein P-glycoprotein, has made it possible to measure levels of MDR1 RNA in human cancers. We report the levels of MDR1 RNA in >400 human cancers. MDR1 RNA levels were usually elevated in untreated, intrinsically drug-resistant tumors, including those derived from the colon, kidney, adrenal gland, liver, and pancreas, as well as in carcinoid tumors, chronic myelogenous leukemia in blast crisis, and cell lines of non-small cell carcinoma of the lung (NSCLC) with neu-roendocrine properties. MDR1 RNA levels were occasionally elevated in other untreated cancers, including neu-roblastoma, acute lymphocytic leukemia (ALL) in adults, acute nonlymphocytic leukemia (ANLL) in adults, and indolent non-Hodgkin's lymphoma. MDR1 RNA levels were also increased in some cancers at relapse after chemotherapy, including ALL, ANLL, breast cancer, neuroblastoma, pheochromocytoma, and nodular, poorly differentiated lymphoma. Many types of drug-sensitive and drug-resistant tumors, including NSCLC and melanoma, contained un-detectable or low levels of MDR1 RNA. The consistent association of MDR1 expression with several intrinsically resistant cancers and the increased expression of the MDR1 gene in certain cancers with acquired drug resistance indicate that the MDR1 gene contributes to multidrug resistance in many human cancers. Thus, evaluation of MDR1 gene expression may prove to be a valuable tool in the identification of individuals whose cancers are resistant to specific agents. The information may be useful in designing or altering chemotherapeutic protocols in these patients. [J Natl Cancer Inst 1989;81:116–124]
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