Regulation of aromatase and sulphatase in breast tumour cells.
In situ oestrogen synthesis makes an important contribution to the high oestrogen concentration found in breast tumours. Cytokines, including interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF alpha), have been shown to regulate aromatase activity in fibroblasts derived from normal and malignant breast tissues. In the present study, the ability of other cytokines in the IL-6 superfamily (IL-11 and oncostatin M) to stimulate aromatase activity has been confirmed. Formation of oestrone via the oestrone sulphatase pathway may be the major route of tumour oestrogen synthesis and in the present study TNF alpha was found to stimulate sulphatase activity in a dose-dependent manner. Human serum albumin was also found to be a potent stimulator of oestrone sulphatase activity. Its stimulatory effect was blocked by basic fibroblast growth factor, but not by several other growth factors tested. Insight into the regulation of oestrogen synthesis in breast tumours should enable the development of novel compounds to inhibit oestrogen synthesis in women with breast cancer.
Purohit
A
A
Unit of Metabolic Medicine, St Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, UK.
Wang
D Y
DY
Ghilchik
M W
MW
Reed
M J
MJ
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001141:Aromatase / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology; D012709:Serum Albumin / Q000494:pharmacology; D013268:Stimulation, Chemical; D013429:Sulfatases / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018931:Antineoplastic Agents, Hormonal; D016207:Cytokines; D004967:Estrogens; D006131:Growth Inhibitors; D017370:Interleukin-11; C508351:OSM protein, human; D010455:Peptides; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D053683:Oncostatin M; D003907:Dexamethasone; D001141:Aromatase; D013429:Sulfatases; C020121:estrone sulfatase