Modulation of oestrone sulphate formation and hydrolysis in breast cancer cells by breast cyst fluid from British and Hungarian women

Abstract

Women with gross cystic breast disease may have an increased risk of breast cancer. In this study the ability of breast cyst fluid (BCF), obtained from British or Hungarian women, to modulate oestrone sulphate (E1S) formation or hydrolysis, has been examined. For this, oestrogen receptor-positive (ER+) MCF-7 or MDA-MB-231 (ER–) breast cancer cells were employed. The formation and hydrolysis of E1S was measured using radiometric techniques. BCF from British and Hungarian women mainly inhibited E1S hydrolysis in MCF-7 cells while stimulating hydrolysis in MDA-MB-231 cells. The extent of inhibition or stimulation of E1S hydrolysis in these cells was related to the Na⁺/K⁺ratio of the BCF. There was a significant inverse relationship between the extent to which BCF samples inhibited hydrolysis in MCF-7 cells and stimulated it in MDA-MB-231 cells. BCF stimulated E1S formation in MCF-7 cells while inhibiting formation in MDA-MB-231 cells. No difference in the ability of BCF from British or Hungarian women to inhibit or stimulate E1S hydrolysis was detected in ER+ or ER– breast cancer cells. In contrast, BCF from British women stimulated E1S formation in ER+ cells (median 82%) to a significantly greater extent (P< 0.01) than BCF from Hungarian women (median 33%). The role that E1S has in breast cancer development remains unclear. The greater stimulation of E1S formation by BCF from British women, who have a higher risk of breast cancer than Hungarian women, suggests that it may act as a storage form of oestrogen within cells that can be activated by oestrone sulphatase. © 2000 Cancer Research Campaign