Topoisomerase I and II activity in human breast, cervix, lung and colon cancer.
The identification of human DNA topoisomerases as cellular targets for active anti-cancer drugs has stimulated further interest in topoisomerase function in tumour biology. Topoisomerase I and II catalytic activity is detectable in many normal and malignant tissues. However, little is known about the expression of topoisomerases in most human solid tumours. The present study evaluated topoisomerase I and II activity in biopsy samples from 86 patients with breast, lung, cervix or colon cancers. Significant intra- and inter-tumour variation in topoisomerase expression was observed. Topoisomerase I activity was relatively high in cervix and colon tumours in comparison to lung and breast cancers. Topoisomerase II activity was high in cervix, colon and lung cancers relative to breast cancer. Topoisomerase I and II activity co-segregated in individual colon tumour samples, but no correlation was observed in cervix, lung or breast tumours. The large heterogeneity in both topoisomerase I and II activity within a tumour type suggests a mechanism for variable response to topoisomerase-directed therapy. The differences in activity between tumour groups suggest that the potential efficacy of inhibitors of topoisomerase I in colon and cervical tumours may be greater than in lung and breast tumours. Future in vivo evaluation is required to establish the clinical relevance of the observed heterogeneity in topoisomerase activity.
CRC Department of Medical Oncology, University of Glasgow, The Netherlands.
H L
HL
McLeod
F
F
Douglas
M
M
Oates
R P
RP
Symonds
D
D
Prakash
A G
AG
van der Zee
S B
SB
Kaye
R
R
Brown
W N
WN
Keith
D001943:Breast Neoplasms / Q000201:enzymology*; D003110:Colonic Neoplasms / Q000201:enzymology*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D018105:DNA, Kinetoplast / Q000378:metabolism; D004278:DNA, Superhelical / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology*; D013539:Simian virus 40 / Q000235:genetics; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000201:enzymology*
D018105:DNA, Kinetoplast; D004278:DNA, Superhelical; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II