REGULATION OF AROMATASE-ACTIVITY WITHIN THE BREAST

Local oestrogen biosynthesis within the breast can be highly variable, in vitro aromatase activity both in breast cancers and mammary adipos e tissue displaying over a 40-fold range between the highest and lowes t levels. Evidence is presented to show that: (i) transcriptional acti vity may influence oestrogen biosynthesis within breast cancers in tha t both aromatase mRNA and STAT nuclear binding are correlated positive ly to in vitro aromatase activity; (ii) the local presence of cancer m ay enhance aromatase activity in particulate fractions and primary fib roblast cultures from mammary adipose tissue; (iii) tumour extracts an d breast cyst fluids may induce aromatase in cultured fibroblasts, the active principles responsible for these effects being incompletely de fined (although the combination of interleukin (IL)-6 and its soluble receptor dramatically enhances aromatase activity, it is unclear wheth er this particular cytokine system can account for the stimulatory eff ects of breast extracts and fluids); (iv) the aromatase activities in both breast cancer and adipose tissues are susceptible to classical ar omatase inhibitors such as aminoglutethimide and 4-hydroxyandrostenedi one (and to newer inhibitors such as CGS16949 and CGS20267 at low nano molar concentrations) but reduced sensitivity to 4-hydroxyandrostenedi one may be observed in certain breast cancers. These findings may have important implications for the development and progression of hormone -dependent cancers within the breast. (C) 1997 Elsevier Science Ltd.