Abstract
Increased expression of the mdr1 gene, encoding the 175 kDa P-glycoprotein, and the gst-pi gene, encoding the anionic isozyme of glutathione S-transferase (GST), have previously been detected in continuous human breast cancer cell lines selected in vitro for resistance to doxorubicin. In this present study we have measured RNA levels of mdr1 and gst-pi in primary human breast tumour biopsies prior to chemotherapy and from tumours which have different inherent responses to doxorubicin treatment, including colon, head and neck squamous cell carcinomas and myeloid leukaemias. Detectable levels of mdr1 mRNA was observed in 25 out of 49 breast tumours, with up to a 100-fold range in expression. A narrower range of gst-pi expression has also been observed in these tumours. Chemosensitivity of cells grown in short-term culture from some of the breast tumours has been measured by an in vitro colony forming assay in the presence of doxorubicin. Comparison of the dose of doxorubicin causing 50% inhibition of growth (ID50) with RNA levels showed that the tumours with high mdr1 expression had high ID50, while the more sensitive explants had low mdr1 expression. These results support a role for mdr1 gene expression in determining the response of human breast cancer cells to chemotherapy.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 24 print issues and online access
$259.00 per year
only $10.79 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Keith, W., Stallard, S. & Brown, R. Expression of mdr1 and gst-π in human breast tumours: comparison to in vitro chemosensitivity. Br J Cancer 61, 712–716 (1990). https://doi.org/10.1038/bjc.1990.160
Issue Date:
DOI: https://doi.org/10.1038/bjc.1990.160
This article is cited by
-
MicroRNAs delivered by extracellular vesicles: an emerging resistance mechanism for breast cancer
Tumor Biology (2014)
-
Prediction of lack of response to neoadjuvant chemotherapy in rare breast tumour histology with Tc-99m sestamibi scintimammography
Annals of Nuclear Medicine (2011)
-
Trabectedin (ET-743, Yondelis™) is a substrate for P-glycoprotein, but only high expression of P-glycoprotein confers the multidrug resistance phenotype
Investigational New Drugs (2007)
-
Prognostic impact of multidrug resistance gene expression on the management of breast cancer in the context of adjuvant therapy based on a series of 171 patients
British Journal of Cancer (2006)
-
Screening of drug resistance-related genes from human ovarian cancer cell line OC3/ADR by DD-PCR
Chinese Journal of Cancer Research (2001)