Expression of multidrug resistance gene in human cancers

Lori J. Goldstein, Hanan Galski, Antonio Fojo, Mark Willingham, Shinn Lian Lai, Adi Gazdar, Robert Pirker, Alexander Green, William Crist, Garrett M. Brodeur, Michael Lieber, Jeffrey Cossman, Michael M. Gottesman, Ira Pastan

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Abstract

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].

Original languageEnglish (US)
Pages (from-to)116-124
Number of pages9
JournalJournal of the National Cancer Institute
Volume81
Issue number2
DOIs
StatePublished - Jan 18 1989

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Goldstein, L. J., Galski, H., Fojo, A., Willingham, M., Lai, S. L., Gazdar, A., Pirker, R., Green, A., Crist, W., Brodeur, G. M., Lieber, M., Cossman, J., Gottesman, M. M., & Pastan, I. (1989). Expression of multidrug resistance gene in human cancers. Journal of the National Cancer Institute, 81(2), 116-124. https://doi.org/10.1093/jnci/81.2.116