Paracrine control of oestrogen production in breast cancer

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Abstract
Breast cancer remains a major cause of death in postmenopausal women. Concentrations of the biologically active oestrogen, oestradiol, are increased in breast tumours and there is now good evidence that cytokines which are present in tumours can stimulate tumour oestrogen synthesis. In this study we have examined the ability of interleukin-6 (IL-6) or tumour necrosis factor α (TNFα), either alone or in combination, to stimulate aromatase, oestradiol dehydrogenase (reductive) or oestrone sulphatase activities in cultured breast cancer cells. Both IL-6 and TNFα were able to stimulate the activities of these enzymes but in combination acted synergistically to markedly enhance enzyme activity. The possibility that α2-macroglobulin might also interact with IL-6 to enhance oestradiol dehydrogenase activity was also examined but no evidence for any synergistic interaction between these two factors was obtained. Cytokines, such as IL-6 and TNFα, are emerging as having a central role in regulating breast tumour oestrogen 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 breast cancer.

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