Tissue-specific transcripts of human steroid sulfatase are under control of estrogen signaling pathways in breast carcinoma.
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 alpha (ERalpha)-positive and ERalpha-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 ERalpha as essential regulator of STS transcription and provide evidence of direct estradiol-dependent binding of ERalpha 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.
Zaichuk
Tetiana
T
Department of Surgery, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA. t-zaichuk@northwestern.edu
Ivancic
David
D
Scholtens
Denise
D
Schiller
Carol
C
Khan
Seema A
SA
D001483:Base Sequence; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000502:physiology; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015398:Signal Transduction; D043266:Steryl-Sulfatase / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology
D017931:DNA Primers; D047628:Estrogen Receptor alpha; D004967:Estrogens; D043266:Steryl-Sulfatase