Steroid sulfatase (STS) contributes to the generation of active estrogens in target tissues by removing the sulfate group from more stable but inactive circulating precursors. Prevention of sulfatase expression in breast tumors or the inhibition of STS activity could provide new strategies to suppression of in situ estrogen biosynthesis. The recently developed treatments that target STS activity highlight the clinical relevance of inhibiting the STS pathway that is enhanced in estrogen receptor α (ER α)-positive breast cancer. Thus, clarifying mechanisms controlling STS expression and function and those that may interfere with its activity is crucial for preserving physiological STS activity while restricting its involvement in pathological processes. Alternative splicing results in several tissue-specific STS mRNA transcripts, which differ in their 5’- regions. We have demonstrated previously that mRNA expression of STS isoforms is inducible by short term treatment with estradiol (E2) in MCF7 cells in an ERα-dependent manner. Dietary phytoestrogens are promoted as alternatives to synthetic estrogens for hormone therapy, however, their effects on the local estrogen biosynthesis have not been exhaustively studied. In the present study we compared the dose-response effect (range: 10-7M to 10-5M) of genistein and resveratrol on the expression of STS mRNAs in cancerous (hormone-dependent MCF-7 and hormone-independent MDA-MB231) and non-malignant MCF10A human mammary epithelial cell lines; the results were compared with that of tibolone, a potent STS inhibitor. We also explored if the ability of studied compounds to affect the cells growth is conferred by changes in STS expression. Our results indicate that the phytochemicals and tibolone can significantly decrease STS mRNA levels, depending on cell line and media composition. However, dose-dependent responses are not present in all cases, suggesting that these compounds are not directly affecting STS gene expression. Downregulation of STS mRNA expression in mammary epithelial cells does not always coincide with decreased proliferation.
99th AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA