Tissue-specific transcripts of human steroid sulfatase are under control of estrogen signaling pathways in breast carcinoma

Tetiana Zaichuk*, David Ivancic, Denise Scholtens, Carol Schiller, Seema A. Khan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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 languageEnglish (US)
Pages (from-to)76-84
Number of pages9
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume105
Issue number1-5
DOIs
StatePublished - Jun 2007

Keywords

  • Breast cancer
  • Estrogen receptor
  • Steroid biosynthesis
  • Steroid sulfatase

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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