Expression of mdr1 and gst-π in human breast tumours: comparison to in vitro chemosensitivity

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.