Molecular analysis of the topoisomerase II α gene and its expression in human ovarian cancer

van der Zee, A.G.J., de Vries, E.G.E., Hollema, H., Kaye, S.B., Brown, R. and Keith, W.N. (1994) Molecular analysis of the topoisomerase II α gene and its expression in human ovarian cancer. Annals of Oncology, 5(1), pp. 75-81. (doi: 10.1093/oxfordjournals.annonc.a058700) (PMID:8172796)

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Abstract

Background: DNA topoisomerase II enzymes are key targets for the group of anti-tumour agents known as topoisomerase inhibitors. In general, cell lines which express high levels of topoisomerase II are sensitive to the cytotoxic effects of the topoisomerase poisons. The levels of topoisomerase II expression in tumour biopsies may therefore predict response to treatment with enzyme inhibitors. In the current study we have analysed ovarian tumours for expression of topoisomerase II a and genetic change at the topoisomerase II a locus on chromosome 17. Materials and methods: We have used methodology which allows the sequential extraction of protein and genomic DNA from the same biopsy sample to study the topoisomerase II α locus and the expression in ovarian cancer. Topoisomerase II α expression was quantified by Western blot analysis in 54 tumours. Results: Topoisomerase II α expression was detected in 65% of ovarian tumours with a 16 fold range in level. In adenocarcinomas, the topoisomerase II α gene can become amplified due to its proximity to ERBB2 on chromosome 17q. Of 86 ovarian tumours studied only 1 had amplification of ERBB2 and none had amplification of topoisomerase II α a sequences. Conclusions: Topoisomerase II α expression was detected in ovarian carcinomas by Western blot analysis. A sixteen-fold range in expression was detected with significantly higher levels of topoisomerase II α expression in advanced stage IV and grade III tumours. Molecular analysis of the topoisomerase II α locus failed to reveal any gross genetic alterations which could account for the variation in levels of expression.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Keith, Professor Nicol and Kaye, Professor Stanley
Authors: van der Zee, A.G.J., de Vries, E.G.E., Hollema, H., Kaye, S.B., Brown, R., and Keith, W.N.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Annals of Oncology
Publisher:Kluwer Academic
ISSN:0923-7534
ISSN (Online):1569-8041

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