Regulation of aromatase activity within the breast

W R Miller, P Mullen, P Sourdaine, C Watson, J M Dixon, J Telford

Research output: Contribution to journalArticlepeer-review


Local oestrogen biosynthesis within the breast can be highly variable, in vitro aromatase activity both in breast cancers and mammary adipose tissue displaying over a 40-fold range between the highest and lowest levels. Evidence is presented to show that: (i) transcriptional activity may influence oestrogen biosynthesis within breast cancers in that both aromatase mRNA and STAT nuclear binding are correlated positively to in vitro aromatase activity; (ii) the local presence of cancer may enhance aromatase activity in particulate fractions and primary fibroblast cultures from mammary adipose tissue; (iii) tumour extracts and breast cyst fluids may induce aromatase in cultured fibroblasts, the active principles responsible for these effects being incompletely defined (although the combination of interleukin (IL)-6 and its soluble receptor dramatically enhances aromatase activity, it is unclear whether this particular cytokine system can account for the stimulatory effects of breast extracts and fluids); (iv) the aromatase activities in both breast cancer and adipose tissues are susceptible to classical aromatase inhibitors such as aminoglutethimide and 4-hydroxyandrostenedione (and to newer inhibitors such as CGS16949 and CGS20267 at low nanomolar concentrations) but reduced sensitivity to 4-hydroxyandrostenedione 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.

Original languageEnglish
Pages (from-to)193-202
Number of pages10
JournalThe Journal of Steroid Biochemistry and Molecular Biology
Issue number3-6
Publication statusPublished - Apr 1997


  • Adipose Tissue/enzymology
  • Aromatase/metabolism
  • Aromatase Inhibitors
  • Breast/enzymology
  • Breast Neoplasms/enzymology
  • Enzyme Inhibitors/pharmacology
  • Female
  • Fibroblasts/enzymology
  • Humans
  • Letrozole
  • Nitriles/pharmacology
  • Triazoles/pharmacology


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