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Analysis of the Expression of MRP, the Gene for a New Putative Transmembrane Drug Transporter, in Human Multidrug Resistant Lung Cancer Cell Lines¹

Division of Molecular Biology, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands [G. J. R. Z., J. J. M. S., E. W. H. M. E., M. H., A. J. S., F. B., P. B.]; Laboratory of Biochemistry, University of Amsterdam [G. J. R. Z.], Department of Medical Oncology, Free University of Amsterdam [C. H. M. V., H. J. B.], and Division of Neurology, Academical Medical Center [F. B.], Amsterdam, the Netherlands; and Division of Medical Oncology, University of Groningen, Groningen, the Netherlands [N. H. M., E. G. E. V.]

Human cells can become multidrug resistant (MDR) by an increase in the activity of the MDR1 P-glycoprotein or by other, as yet unknown mechanisms, referred to as non-P-glycoprotein mediated MDR (non-Pgp MDR). S. P. C. Cole et al. [Science (Washington DC), 258: 1650–1654, 1992] recently reported that in two cell lines non-Pgp MDR was associated with the overexpression of a new putative membrane transporter gene, MRP. Using an RNase protection assay we have analyzed the expression of MRP in non-Pgp MDR sublines of the human lung cancer cell lines SW-1573 (non-small cell lung cancer) and GLC4 (small cell lung cancer). In all of ten SW-1573 derived lines examined the MRP mRNA level was equal to that in the parental line, whereas MRP was 25-fold overexpressed in a resistant subline of GLC4. We conclude that overexpression of MRP cannot account for all forms of non-Pgp MDR.

¹ This work was supported by a collaborative project of the Netherlands Cancer Institute and the Laboratory of Biochemistry, University of Amsterdam (G. J. R. Z.), and by a grant from the Dutch Cancer Society (NKI 91-18 to F. B. and P. B.).

² To whom requests for reprints should be addressed.

Received 2/ 9/93. Accepted 3/15/93.

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