title: Regulation of aromatase activity within the breast.
abstract: 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.
authors.affiliation: University Dept. of Clinical Oncology, Western General Hospital, Edinburgh, U.K.
authors.forename: W R
authors.initials: WR
authors.lastname: Miller
authors.forename: P
authors.initials: P
authors.lastname: Mullen
authors.forename: P
authors.initials: P
authors.lastname: Sourdaine
authors.forename: C
authors.initials: C
authors.lastname: Watson
authors.forename: J M
authors.initials: JM
authors.lastname: Dixon
authors.forename: J
authors.initials: J
authors.lastname: Telford
mesh_terms: D000273:Adipose Tissue / Q000201:enzymology; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors; D001940:Breast / Q000201:enzymology* / Q000473:pathology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D000077289:Letrozole; D009570:Nitriles / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
chemical_list: D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole; D001141:Aromatase