1. ¹Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK
2. ²Department of Medical Oncology, University of Glasgow, Switchback Road, Glasgow G61 1BD, UK

Correspondence: Dr W Wang, Beatson Laboratories for Cancer Research, Garscube Estate, Bearsden, Glasgow G61 1BD, UK. E-mail: w.wang@beatson.gla.ac.uk

Received 19 July 2002; Revised 6 November 2002; Accepted 8 November 2002.

Abstract

In this study, the gene copy number, mRNA and protein expression levels and nuclear DNA-binding activity of nuclear factor kappa B (NF-B) were compared in a panel of five pairs of thymidylate synthase (TS) inhibitor-resistant and wild-type parent cancer cell lines. High constitutive NF-B DNA-binding activity was detected in all chemoresistant cell lines. The upregulated NF-B activity was composed of NF-B subunits p50 and p65. Four out of five resistant cell lines constitutively overexpressed NF-B p50 and p65 mRNA and protein. One resistant cell line with the highest NF-B DNA-binding activity showed normal p50 and p65 protein expression. No NF-B gene amplification was detected in resistant cell lines. Transient exposure of wild-type RKO_WT and H630_WT cells to 5-FU induced NF-B DNA-binding activity but had no effect on NF-B protein expression in these cells. Our results indicate that high constitutive NF-B activity caused by its gene overexpression is an intrinsic character of TS inhibitor-resistant cells. NF-B can antagonise anticancer drug-induced apoptosis. High NF-B expression and nuclear activity in TS inhibitor-resistant cancer cells may play an important role in the chemoresistance.