Abstract
Steroid sulfatase (STS) increases the pool of precursors of biologically active steroids, thereby playing an important role in breast cancer development. Mechanisms that control STS expression remain poorly understood. In present study we investigated alterations in the 5′ region of STS gene to gain insight into the mechanism(s) that regulates its expression in mammary epithelial cells. We found that at least four alternatively spliced transcripts of STS gene can be produced from at least four different leader exons. Distinct expression patterns of the STS variants were observed in human tissues. Expression profiles of estrogen receptor α (ERα)-positive and ERα-negative breast carcinomas showed that these two categories of tumors and their adjacent benign tissues display remarkably different expression of STS isoforms. Coexpression of STS isoforms with ER isotypes suggests their cell-type specific coregulation. In addition, we identified ERα as essential regulator of STS transcription and provide evidence of direct estradiol-dependent binding of ERα to multiple STS cis-regulatory regions in vivo. Our results indicate that STS isoforms are under control of estrogen signaling pathways and their differential expression may play a significant role in breast cancer biology.
Original language | English (US) |
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Pages (from-to) | 76-84 |
Number of pages | 9 |
Journal | Journal of Steroid Biochemistry and Molecular Biology |
Volume | 105 |
Issue number | 1-5 |
DOIs | |
State | Published - Jun 2007 |
Funding
We thank Drs. C. Waltenbaugh, A. Chlenski, and A. Levenson for providing critical comments on the manuscript, and Dr. D. Patil and Mr. E. Schilling for technical assistance. This work was supported by the Bluhm Family Program for Breast Cancer Early Detection & Prevention and NIH/NCI P50 CA89018-02 .
Keywords
- Breast cancer
- Estrogen receptor
- Steroid biosynthesis
- Steroid sulfatase
ASJC Scopus subject areas
- Endocrinology
- Molecular Medicine
- Molecular Biology
- Biochemistry
- Clinical Biochemistry
- Endocrinology, Diabetes and Metabolism
- Cell Biology