Regulation of steroid sulphatase expression and activity in breast cancer

Steroid sulphatase (STS) catalysis the conversion of oestrone sulphate (EIS) to oestrone (Ei) and irs action in breast rumours makes a major contribution to in situ oestrogen production in this tissue, Although expression of STS mRNA and STS activity are increased in malignant breast tissues compared with that ill non-malignant tissues, little is known about the regulation of its expression or activity. In the present study we have used a RT-PCR technique to investigate the regulation of STS mRNA expression in cultured breast tissue fibroblasts and MCF-7 cells. STS mRNA expression was readily detectable in fibroblasts derived from breast tissue proximal to rumours, breast tumour tissue and reduction mammoplasty tissue. For two pre-menopausal subjects. STS mRNA expression was similar in proximal and tumour fibroblasts whereas for a third, post-menopausal subject, expression in breast tumour fibroblasts was 2-4-fold that in proximal fibroblasts. The cytokine tumour necrosis factor alpha (TNF alpha) or the STS inhibitor. 3-methoxyorstrone-3-O-sulphamate. had no effect on STS mRNA expression in fibroblasts. STS mRNA was detectable in MCF-7 cells but neither TNF alpha nor interleukin 6 (IL-6) affected its expression. Transient transfection of COS-1 and MCF-7 cells with a STS cDNA lacking STS 5' and 3' sequences increased activity 17-fold and 2-fold, respectively. TNF alpha plus IL-6 increased STS activity in mock transfected MCF-7 cells and further increased STS activity in transfected MCF-7 cells. This indicates that activation can occur independently of STS promoter and enhancer elements. in conjunction with the lack of regulation of STS mRNA it suggest that TNF alpha and IL-6 may increase STS activity via a post-translational modification of the enzyme or by increasing substrate availability. (C) 2001 Elsevier Science Ltd. All rights reserved.