Gross cystic breast disease frequently occurs in premenopausal women and women with apocrine cysts may have an increased risk of developing breast cancer. Many steroids, growth factors, cytokines and proteins have now been identified in breast cyst fluid (BCF), but it is not yet known whether any of these factors may be associated with an increased risk for cancer, or if these factors have a functional role within the breast. In this study we show that concentrations of the cytokine interleukin-2 are higher in BCF with a low electrolyte ratio, whereas albumin concentrations are increased in BCF with a high Na+/K+ ratio. As albumin has been shown to potentiate the ability of growth factors, such as insulin-like growth factor-I (IGF-I), to stimulate oestradiol-17β hydroxysteroid dehydrogenase (E2DH) (reductive) activity in breast cancer cells, we have examined the ability of other proteins which are found in breast secretions (α-lactalbumin, lactoferrin) or BCF (gross cystic disease proteins-15 and -24) to potentiate the action of this growth factor. While lactoferrin had no effect on E2DH, the other proteins tested significantly potentiated the effect of IGF-I on the activity of this enzyme. Recombinant human albumin also acted synergistically with IGF-I to stimulate E2DH activity, suggesting that the ability of albumin to potentiate growth factor action is an intrinsic property of the molecule itself, rather than being due to the presence of a ligand which is bound to the molecule. Results from these investigations suggest that proteins found in breast secretions and BCF may have a functional role in regulating oestrogen synthesis in breast tissues.
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