Insulin-like growth factor type I and insulin-like growth factor type II stimulate oestradiol-17 beta hydroxysteroid dehydrogenase (reductive) activity in breast cancer cells.
Oestradiol-17 beta hydroxysteroid dehydrogenase (E2DH) is present in normal and malignant breast tissues and also in cultured breast cancer cells. It can act in a reductive direction to convert oestrone to the biologically active oestrogen, oestradiol, or in an oxidative direction to metabolize oestradiol to oestrone and may therefore have a crucial role in regulating breast tissue concentrations of oestradiol. Insulin-like growth factor-type I (IGF-I) and IGF-II are both mitogens for breast cancer cells. In this study we have examined the effect of these growth factors on the reductive and oxidative activities of E2DH in MCF-7 (receptor positive) and MDA-MB-231 (receptor negative) breast cancer cells. Both IGF-I (80 ng/ml) and IGF-II (80 ng/ml) significantly stimulated E2DH reductive activity (up to 138%) in MCF-7 cells but had no effect on oxidative activity. Addition of IGF-II (100 ng/ml) to MDA-MB-231 cells resulted in a small but statistically significant (p less than 0.05) increase in E2DH reductive activity (18%) but in these cells reductive activity is 25-70 times lower than oxidative activity. If IGF-I and IGF-II act to stimulate E2DH reductive activity in breast tumours then such a mechanism could account for the increased concentrations of oestradiol detected in breast tumours.
Singh
A
A
Unit of Metabolic Medicine, St Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London.
Reed
M J
MJ
D001943:Breast Neoplasms / Q000201:enzymology*; D002460:Cell Line; D004960:Estradiol Dehydrogenases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D007335:Insulin-Like Growth Factor II / Q000502:physiology*; D010084:Oxidation-Reduction; D014407:Tumor Cells, Cultured / Q000201:enzymology
D007328:Insulin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D004960:Estradiol Dehydrogenases