The regulation of aromatase activity in breast fibroblasts: the role of interleukin-6 and prostaglandin E2.
Prostaglandin E2 (PGE2) and cytokines, such as interleukin-6 (IL-6) or tumour necrosis factor a (TNFalpha) can regulate aromatase activity. In the present study we have compared their abilities to stimulate aromatase activity in fibroblasts derived from 'normal' breast adipose tissue proximal to a tumour or breast tumours. PGE2, TNFalpha and IL-6 plus its soluble receptor (IL-6sR) all increased aromatase activity in these cells. Basal aromatase activity and the degree of aromatase stimulation by these factors were greater in fibroblasts derived from 'normal' breast tissue than from breast tumours. The ability of IL-6+IL-6sR to increase aromatase activity was only marginally reduced by the PG synthesis inhibitor, indomethacin, indicating that IL-6+IL-6sR does not appear to act via induction of PG synthesis. The ability of PGE2 to stimulate aromatase activity in fibroblasts derived from 'normal' breast tissue was potentiated by IL-6sR suggesting that PGE2 may act via induction of IL-6. This was confirmed by measurement of IL-6 in conditioned medium collected from these cells. A significant increase in IL-6 concentrations was detected in conditioned medium collected from cells treated with PGE2. It is concluded that in some fibroblasts PGE2 may exert part of its regulatory effect on breast tissue aromatase activity via induction of IL-6.
Singh
A
A
Endocrinology and Metabolic Medicine, Imperial College School of Medicine, St. Mary's Hospital, London, UK.
Purohit
A
A
Ghilchik
M W
MW
Reed
M J
MJ
D000273:Adipose Tissue / Q000201:enzymology; D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D001940:Breast / Q000201:enzymology*; D001943:Breast Neoplasms / Q000201:enzymology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000502:physiology*; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D001141:Aromatase; D015232:Dinoprostone