PARACRINE CONTROL OF ESTROGEN PRODUCTION IN BREAST-CANCER

Breast cancer remains a major cause of death in postmenopausal women. Concentrations of the biologically active oestrogen, oestradiol, are i ncreased in breast rumours and there is now good evidence that cytokin es which are present in rumours can stimulate tumour oestrogen synthes is. In this study we have examined the ability of interleukin-6 (IL-6) or tumour necrosis factor alpha (TNF alpha), either alone or in combi nation, to stimulate aromatase, oestradiol dehydrogenase (reductive) o r oestrone sulphatase activities in cultured breast cancer cells. Both IL-6 and TNF alpha were able to stimulate the activities of these enz ymes but in combination acted synergistically to markedly enhance enzy me activity. The possibility that alpha(2)-macroglobulin might also in teract with IL-6 to enhance oestradiol dehydrogenase activity was also examined but no evidence for any synergistic interaction between thes e two factors was obtained. Cytokines, such as IL-6 and TNF-alpha, are emerging as having a central role in regulating breast tumour oestrog en synthesis. Understanding the role that cytokines have in regulating oestrogen synthesis in breast tumours should lead to the development of novel therapeutic agents for use in the treatment of women with bre ast cancer.