Oestrogen formation in breast: clinical and biological importance.
It has been known for many years that many breast carcinomas can synthesize oestrogens from androgens via the action of the enzyme aromatase. There has been widespread speculation on the possibility that this acts as an important intracrine source of growth stimulation. For example, there are data which indicate that clinical response to aromatase inhibitors is far more common in tumours which possess measurable amounts of aromatase. In addition, aromatase activity in the quadrant of the normal breast surrounding breast carcinomas is generally higher than in the other quadrants. However, these data are only suggestive and the case for a significant role for intratumoural aromatase in breast cancer growth remains unproven. We have recently explored this possibility by the transfection of human breast cancer cells with aromatase. By a series of experiments in athymic mice we have demonstrated that growth is supported by this intracrine source in the absence of endocrine oestrogen stimulation.
Dowsett
M
M
Royal Marsden Hospital, London, UK.
Detre
S
S
Rowlands
M
M
Grimshaw
R
R
D000735:Androstenedione / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D047072:Aromatase Inhibitors; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D000077289:Letrozole; D051379:Mice; D008819:Mice, Nude; D009570:Nitriles / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection; D014230:Triazoles / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004967:Estrogens; D009570:Nitriles; D014230:Triazoles; D000735:Androstenedione; D000077289:Letrozole; D001141:Aromatase; C014594:formestane