Journal of Clinical Oncology, Vol 5, 1922-1927, Copyright © 1987 by American Society of Clinical Oncology
Intrinsic drug resistance in human kidney cancer is associated with expression of a human multidrug-resistance gene
AT Fojo, DW Shen, LA Mickley, I Pastan and MM Gottesman
Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
The cloning of the cDNA for the mdr1 gene, whose expression is associated
with the development of multidrug-resistance in cultured cells, has made it
possible to explore the mechanism of multidrug resistance in human tumors.
We have found that normal human kidney, six of eight adenocarcinomas of the
kidney, and four cell lines derived from kidney adenocarcinomas express
high levels of mdr1 mRNA. Two criteria suggest that primary multidrug
resistance in human adenocarcinomas of the kidney results, at least in
part, from expression of the mdr1 gene: (1) mdr1 mRNA levels are elevated
in four unselected kidney adenocarcinoma cell lines that show a multidrug-
resistant phenotype; and (2) multidrug resistance in these kidney cancer
cell lines is reversed by verapamil and quinidine, agents known to reverse
mdr1-associated drug resistance in cell lines selected for multidrug
resistance in vitro. These results suggest that appropriate pharmacological
intervention to reverse multidrug resistance might make adenocarcinomas of
the kidney more sensitive to chemotherapy with agents such as Adriamycin
(Adria Laboratories, Columbus, OH) and the vinca alkaloids.
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