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

Zaichuk, Tetiana; Ivancic, David; Scholtens, Denise M.; Schiller, Carol L.; Khan, Seema A.

doi:10.1016/j.jsbmb.2006.12.101

Cited by 27 publications

(31 citation statements)

References 41 publications

(48 reference statements)

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“…Exon 1c, previously found in thyroid and peripheral mononuclear leukocytes, is expressed in all tissues analysed, except arthrosic cartilage of the femoral head, but always at very low levels. These results are in agreement with those of previous works [14,15]. Exon 1d and particularly exon 1e were expressed in a restricted number of tissues and at low expression levels.…”

Section: Rt-mlpa Analysissupporting

confidence: 94%

“…Only exons 1a, associated with the promoter that drives expression in placenta, and 1b, that presents the broadest tissue distribution, are partially coding with putative ATGs in frame with another ATG in exon 2. Four alternatively spliced STS transcripts that differ at their first exons were also identified in MCF-7 mammary epithelial cells by Zaichuk et al [15]. These transcripts, that correspond to those previously identified [13,14], were shown to have distinct expression patterns in human tissues and in different categories of breast tumors, suggesting cell-type-specific co-regulation.…”

Section: Introductionmentioning

confidence: 53%

“…In some tissues, no STS transcripts containing the first exon 1a (the placental one) could be found, thus strengthening the hypothesis of a tissue-specific control of transcription. Recently, the study by Zaichuk et al showed that, in breast carcinoma, steroid sulfatase transcription is under the control of estrogen and is up-regulated by 17␤-estradiol via direct binding of the estrogen receptor to estrogen response elements (EREs) located in the promoter regions driving 1a and 1b transcripts [15]. According to the authors, the diversity in the distribution of STS variants among human breast carcinomata presumably reflects specific regulation and function of each of the isoform during tumor progression.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Transcriptional control of human steroid sulfatase

Nardi

Pomari

Zambon

et al. 2009

The Journal of Steroid Biochemistry and Molecular Biology

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Section: Rt-mlpa Analysissupporting

confidence: 94%

Section: Introductionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Transcriptional control of human steroid sulfatase

Nardi

Pomari

Zambon

et al. 2009

The Journal of Steroid Biochemistry and Molecular Biology

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“…Alternative first exons in the STS gene have been recently described in adrenal and other tissues and the STS gene splicing profile differs among tissues. [28][29][30] Indeed, it has been reported that the first exon of the STS mRNA in PC-3 cells is mainly encoded by exon 1a whereas that in skin is mainly encoded by exon 1b. 30) A difference in the STS gene splicing profile might play a key role in the cell-type specific regulation of STS gene expression by cytokines.…”

Section: Discussionmentioning

confidence: 99%

Interferon Gamma Induces Steroid Sulfatase Expression in Human Keratinocytes

Hattori

Yamaguchi

Umezawa

et al. 2012

Biological & Pharmaceutical Bulletin

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Key words steroid sulfatase; keratinocyte; interferon gamma; nuclear factor-kappa B; dexamethasone Steroid sulfatase (STS) is a microsomal enzyme that catalyzes the hydrolysis of sulfated 3-hydroxysteroids to the corresponding free active 3-hydroxysteroids.1) This enzyme is widely distributed throughout the body, and its actions are implicated in both physiological processes and pathological conditions. In many peripheral organs such as skin STS play a key role in the production of dehydroepiandrosterone (DHEA) from DHEA sulfate, which is abundant in the circulation. DHEA is then used as a major precursor for the synthesis of potent androgens in the skin.2) Early studies in vitro and in vivo have shown that the human STS activity appears in specific skin types, such as in foreskin and infantile abdominal skin, after birth.3) It also has been shown that STS plays an important functional role in the skin as this enzyme is deficient in X-linked ichthyosis (X-LI). 4,5) It has been further demonstrated that both the expression of STS mRNA and its enzymatic activity are increased in malignant breast and endometrial tissues compared with nonmalignant tissues and that this increased STS affects active estrogen levels within cells by hydrolysis of inactive estrogen sulfates. 6) We recently reported that estradiol sulfate, whose formation is catalyzed by estrogen sulfotransferase, is a major metabolite of estradiol in human epidermal keratinocytes. 7) Since estrogens have a significant effect on skin differentiation and development, 8,9) the activity of STS, as well as of estrogen sulfotransferase in the skin must be properly regulated to maintain cutaneous homeostasis. However, little is known about the regulation of STS gene expression or activity in skin.It has been reported previously that interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα) act synergistically to increase STS activity in breast cancer cells, 10,11) and that this effect on STS activity is regulated by posttranslational modification of a cysteine residue in the catalytically active site of this enzyme to formyl glycine. In contrast, the inflammatory cytokine IL-1β decreases STS activity and the expression of STS mRNA in human endometrial stromal cells.12) In psoriatic plaques in skin, there is a predominance of T helper 1 cytokines, most notably interferon gamma (IFNγ).13) IFNγ is a cytokine that is produced by activated T cells and natural killer cells, and induces a variety of effects including anti-viral responses, cell growth and differentiation. 14) In the skin, IFNγ is known to play a pivotal role in the development of inflammatory and immune responses. [15][16][17] However, no information is available concerning the effect of IFNγ on STS expression. IFNγ has been reported to stimulate involucrin gene expression via STAT1 signaling in cells of the SVHK cell line that was established from SV40-transformed human keratinocytes. 18,19) To determine the effect of IFNγ on STS expression in the human epidermis, we investigated the effects of IFNγ...

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“…Several groups report elevated STS expression and activity in cancerous breast tissue in comparison to non-malignant breast tissue [6,8]. Additionally, Zaichuk et al [9] demonstrate that STS expression is elevated only in estrogen receptor (ER)α-positive breast cancer while it is even lowered in ERα-negative cancer tissues. Comparisons of STS versus aromatase activities have attached great importance to the sulfatase pathway [10].…”

Section: Androgen-converting Enzymes In the Breastmentioning

confidence: 99%

The Role of Androgens in Normal and Malignant Breast Tissue

Tiefenbacher

Daxenbichler²

2008

Breast Care

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Androgens, like estrogens, can be synthesized in the breast. As both active androgens and their corresponding receptors are present in breast tissue, we conclude that they play a role in breast physiology. This is supported by the fact that insufficient androgen production or sensitivity results in the development of gynecomastia. Complete androgen insensitivity due to receptor defects leads to normal female breast development in these XY women. While breast development is completely inhibited by male testosterone levels, partial but not total degradation of a developed breast by androgen treatment appears to be possible. Breast cancer in early stages seems to fulfill the prerequisites of androgen responsiveness. Androgen treatment of advanced breast cancer has shown similar effectiveness as anti-estrogen or estrogen-ablative therapy, but also considerable side effects. It has been speculated that the use of selective androgen modulators (SARMs), either alone or preferably in addition to anti-estrogens or aromatase inhibitors, may be a promising alternative to current therapy modalities in hormone-dependent breast cancer. In addition, future studies on the use of SARMs in prophylactic settings seem to be justified.

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

Cited by 27 publications

References 41 publications

Transcriptional control of human steroid sulfatase

Transcriptional control of human steroid sulfatase

Interferon Gamma Induces Steroid Sulfatase Expression in Human Keratinocytes

The Role of Androgens in Normal and Malignant Breast Tissue

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