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Mechanisms of MRP over-expression in four human lung-cancer cell lines and analysis of the MRP amplicon by Elisabeth W. H. M. Eijdems; Marcel de Haas; José M. Coco-Martin; Cecile P. E. Ottenheim; Guido J. R. Zaman; Hans G. Dauwerse; Martijn H. Breuning; Peter R. Twentyman; Piet Borst; Frank Baas is a Medicine article available to read on EtoBox.

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## Abstract Some multidrug resistant cell lines over‐express the gene encoding the multidrug‐resistance‐associated protein (MRP). In all cell lines reported thus far, over‐expression is associated with gene amplification. We have studied the predominant mechanisms of MRP over‐expression in 4 human lung‐cancer cell lines that cover a range of drug‐resistance levels, and we have analyzed the MRP amplicon. In the SW‐1573‐derived, weakly resistant cell line 30.3M, __MRP__ mRNA is elevated 3‐fold in the absence of gene amplification. Run‐on analysis shows that the increased MRP gene expression in this cell line is due to transcriptional activation. In the highly resistant GLC4/ADR and COR‐L23/R cells, __MRP__ gene amplification predominates, whereas in the moderately resistant MOR/R cells, gene amplification is combined with a mechanism resulting in an additional increase in the level of __MRP__ mRNA. Fluorescence __in situ__ hybridization shows that, in the GLC4/ADR cells, amplified __MRP__ sequences are present both in double minute chromosomes (DM) and in homogeneously staining regions (HSR). By pulsed‐field gel electrophoresis we show that the __MRP__‐containing DM are 1 Mb in lengt

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Author

Elisabeth W. H. M. Eijdems; Marcel de Haas; José M. Coco-Martin; Cecile P. E. Ottenheim; Guido J. R. Zaman; Hans G. Dauwerse; Martijn H. Breuning; Peter R. Twentyman; Piet Borst; Frank Baas

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley; Research Square; Test accounts (ISSN 0020-7136)

Published

1995

Language

EN

Field

Medicine (Health Sciences)