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High level expression of the multidrug resistance (MDR1) gene in the normal bladder urothelium: A potential involvement in protection against carcinogens?

Lookup NU author(s): Professor Steven Clifford, Professor David Neal, Professor John Lunec

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Abstract

It has been suggested that expresssion of the P-glycoprotein transmembrane efflux pump (PGP), encoded by the multidrug resistance (MDR1) gene, may play a role in the protection of epithelial tissues from a variety of local and systemic toxins. We report that in ~50% (6/11) of the population, MDR1 messenger RNA levels in the normal urinary epithelium are comparable to those found in the highest expressing tissues in the body, and suggest a role for PGP in the normal bladder urothelium. MDR1 mRNA levels in the normal urothelium do, however, vary over a 60-fold range between individuals, and furthermore are uniformly significantly lower (~6-fold, P ≤ 0.01) in all low-grade bladder carcinoma samples. On the basis of these observations we conclude that low MDR1 mRNA levels are a uniformly consistent characteristic of low-grade bladder tumours, and hypothesize that high MDR1 expression plays a role in protection of the normal bladder from carcinogen exposure, and that individuals with low normal bladder MDR1 mRNA levels may consequently be at an increased risk of developing bladder cancer. Furthermore, the low level of MDR1 expression generally found in low grade superficial tumours may predispose them to additional carcinogen exposure and in this way contribute to possible tumour progression. In addition, MDR1 mRNA levels were observed to be elevated in a significant proportion (~25%, 8/30, P = 0.015) of high grade tumours compared to low grade samples, and may therefore represent a marker of bladder tumour progression.


Publication metadata

Author(s): Clifford SC, Neal DE, Lunec J

Publication type: Article

Publication status: Published

Journal: Carcinogenesis

Year: 1996

Volume: 17

Issue: 3

Pages: 601-604

Print publication date: 01/03/1996

ISSN (print): 0143-3334

ISSN (electronic): 1460-2180

URL: http://dx.doi.org/10.1093/carcin/17.3.601

DOI: 10.1093/carcin/17.3.601

PubMed id: 8631151


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