Nuclear localization and increased levels of transcription factor YB-1 in primary human breast cancers are associated with intrinsic MDR1 gene ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1997-04

AUTHORS

R C Bargou, K Jürchott, C Wagener, S Bergmann, S Metzner, K Bommert, M Y Mapara, K J Winzer, M Dietel, B Dörken, H D Royer

ABSTRACT

Breast cancers are either primarily resistant to chemotherapy (intrinsic resistance), or respond to chemotherapy but later recur with a multidrug-resistant phenotype because of overexpression of the multidrug transporter P-glycoprotein. The MDR1 gene encoding P-glycoprotein may be transcriptionally regulated by a Y-box transcription factor. We now report that, in multidrug-resistant MCF-7 breast cancer cells, nuclear localization of YB-1 is associated with MDR-1 gene expression. In drug-sensitive MCF-7 cells, however, YB-1 was localized to the cytoplasm. Regulated overexpression of YB-1 in drug-sensitive diploid breast epithelial cells induced MDR-1 gene expression and multidrug resistance. In 27 out of 27 untreated primary breast cancers, YB-1 protein was expressed in the cytoplasm although it was undetectable in normal breast tissue of these patients. In a subgroup of tumors (9/27), however, YB-1 was also localized to the nucleus and, in these cases, high levels of P-glycoprotein were present. These results show that in a subset of untreated primary breast cancers, nuclear localization of YB-1 protein is associated with intrinsic multidrug resistance. Our data show that YB-1 has an important role in controlling MDR1 gene transcription and this finding provides a basis for the analysis of molecular mechanisms responsible for intrinsic multidrug resistance in human breast cancer. More... »

PAGES

447-450

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nm0497-447

DOI

http://dx.doi.org/10.1038/nm0497-447

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1033417633

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/9095180


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