Induction of steroid sulfatase expression in PC-3 human prostate cancer cells by insulin-like growth factor II

Sung, Chul-Hoon; Im, Hee-Jung; Park, Nahee; Kwon, Yeo‐Jung; Shin, Sungho; Ye, Dong-Jin; Cho, Nam-Hyeon; Park, Young-Shin; Choi, Hyung‐Kyoon; Kim, Donghak; Chun, Young‐Jin

doi:10.1016/j.toxlet.2013.09.006

Cited by 11 publications

(4 citation statements)

References 37 publications

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“…In the present study, the level of IGF2 mRNA was shown to be significantly upregulated by IMP3 overexpression (our RNA sequencing data in S5 Table ). IGF-II was shown to induce steroid sulfatase expression via a PI3-kinase/Akt-NF-κB signaling pathway in PC-3 cells and may induce estrogen-mediated carcinogenesis [ 30 ]. However, whether IMP3 regulation of NF-κB signaling pathway is mediated by IGF2 warrants future investigations.…”

Section: Discussionmentioning

confidence: 99%

Enhanced IMP3 Expression Activates NF-кB Pathway and Promotes Renal Cell Carcinoma Progression

Pei

Zhan

et al. 2015

PLoS ONE

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BackgroundInsulin-like growth factor 2 mRNA binding protein 3 (IMP3) is expressed in metastatic and a subset of primary renal cell carcinoma (RCC). However, the role of IMP3 in RCC progression was poorly understood. We aim to uncover the mechanism of IMP3 in regulating clear cell RCC (CCRCC) progression and validate the prognostic significance of IMP3 in localized CCRCC.MethodsCaki-1 cells stably overexpressing IMP3 and Achn cells with knockdown of IMP3 were analyzed for cell migration and invasion by Transwell assay. RNA-seq was used to profile gene expression in IMP3-expressing Caki-1 cells. A cohort of 469 localized CCRCC patients were examined for IMP3 expression by immunohistochemistry using tumor tissue array.ResultsIMP3 promoted Caki-1 cell migration and invasion, whereas knockdown of IMP3 by RNAi inhibited Achn cell migration and invasion. Enhanced IMP3 expression activated NF-кB pathway and through which, it functioned in promoting the RCC cell migration. IMP3 expression in localized CCRCC was found to be associated with higher nuclear grade, higher T stage, necrosis and sarcomatoid differentiation (p< 0.001). Enhanced IMP3 expression was correlated with shorter recurrence-free and overall survivals. Multivariable analysis validated IMP3 as an independent prognostic factor for localized CCRCC patients.ConclusionIMP3 promotes RCC cell migration and invasion by activation of NF-кB pathway. IMP3 is validated to be an independent prognostic marker for localized CCRCC.

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Section: Discussionmentioning

confidence: 99%

Enhanced IMP3 Expression Activates NF-кB Pathway and Promotes Renal Cell Carcinoma Progression

Pei

Zhan

et al. 2015

PLoS ONE

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“…They further demonstrated that at least part of this effect was via the phosphatidylinositol 3 (PI3)-kinase/Akt pathway because PI3-kinase inhibitors and AKT inhibitors suppressed STS mRNA up-regulation induced by TNFα. The same group later examined PC-3 cells and found that IGF-2 increased STS expression via the same PI3-kinase/Akt pathway ( 327 ).…”

Section: Dysregulation Of Steroid Sulfation and Desulfationmentioning

confidence: 99%

The Regulation of Steroid Action by Sulfation and Desulfation

et al. 2015

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Steroid sulfation and desulfation are fundamental pathways vital for a functional vertebrate endocrine system. After biosynthesis, hydrophobic steroids are sulfated to expedite circulatory transit. Target cells express transmembrane organic anion-transporting polypeptides that facilitate cellular uptake of sulfated steroids. Once intracellular, sulfatases hydrolyze these steroid sulfate esters to their unconjugated, and usually active, forms. Because most steroids can be sulfated, including cholesterol, pregnenolone, dehydroepiandrosterone, and estrone, understanding the function, tissue distribution, and regulation of sulfation and desulfation processes provides significant insights into normal endocrine function. Not surprisingly, dysregulation of these pathways is associated with numerous pathologies, including steroid-dependent cancers, polycystic ovary syndrome, and X-linked ichthyosis. Here we provide a comprehensive examination of our current knowledge of endocrine-related sulfation and desulfation pathways. We describe the interplay between sulfatases and sulfotransferases, showing how their expression and regulation influences steroid action. Furthermore, we address the role that organic anion-transporting polypeptides play in regulating intracellular steroid concentrations and how their expression patterns influence many pathologies, especially cancer. Finally, the recent advances in pharmacologically targeting steroidogenic pathways will be examined.

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“…On the other hand, IL6 and tumor necrosis factor (TNF)α increased STS activity in a breast cancer cell line MCF7 not changing the mRNA levels, which suggested posttranslational modifications via STS glycosylation (Newman et al, 2000 ). In contrast, Sung et al recently reported that in prostate cancer cell line PC-3 both, TNFα and insulin growth factor II regulate STS expression at the transcriptional level (Sung et al, 2013 ). STS expression is also regulated by micro (mi)RNA, as the overexpression of miR-142-3p significantly reduced STS mRNA levels in the St-T1b human endometrial stromal cell line (Kästingschäfer et al, 2015 ).…”

Section: Steroid Sulfatasementioning

confidence: 94%

The Important Roles of Steroid Sulfatase and Sulfotransferases in Gynecological Diseases

Rižner

2016

Front. Pharmacol.

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Gynecological diseases such as endometriosis, adenomyosis and uterine fibroids, and gynecological cancers including endometrial cancer and ovarian cancer, affect a large proportion of women. These diseases are estrogen dependent, and their progression often depends on local estrogen formation. In peripheral tissues, estrogens can be formed from the inactive precursors dehydroepiandrosterone sulfate and estrone sulfate. Sulfatase and sulfotransferases have pivotal roles in these processes, where sulfatase hydrolyzes estrone sulfate to estrone, and dehydroepiandrosterone sulfate to dehydroepiandrosterone, and sulfotransferases catalyze the reverse reactions. Further activation of estrone to the most potent estrogen, estradiol, is catalyzed by 17-ketosteroid reductases, while estradiol can also be formed from dehydroepiandrosterone by the sequential actions of 3β-hydroxysteroid dehydrogenase-Δ4-isomerase, aromatase, and 17-ketosteroid reductase. This review introduces the sulfatase and sulfotransferase enzymes, in terms of their structures and reaction mechanisms, and the regulation and different transcripts of their genes, together with the importance of their currently known single nucleotide polymorphisms. Data on expression of sulfatase and sulfotransferases in gynecological diseases are also reviewed. There are often unchanged mRNA and protein levels in diseased tissue, with higher sulfatase activities in cancerous endometrium, ovarian cancer cell lines, and adenomyosis. This can be indicative of a disturbed balance between the sulfatase and sulfotransferases enzymes, defining the potential for sulfatase as a drug target for treatment of gynecological diseases. Finally, clinical trials with sulfatase inhibitors are discussed, where two inhibitors have already concluded phase II trials, although so far with no convincing clinical outcomes for patients with endometrial cancer and endometriosis.

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Induction of steroid sulfatase expression in PC-3 human prostate cancer cells by insulin-like growth factor II

Cited by 11 publications

References 37 publications

Enhanced IMP3 Expression Activates NF-кB Pathway and Promotes Renal Cell Carcinoma Progression

Enhanced IMP3 Expression Activates NF-кB Pathway and Promotes Renal Cell Carcinoma Progression

The Regulation of Steroid Action by Sulfation and Desulfation

The Important Roles of Steroid Sulfatase and Sulfotransferases in Gynecological Diseases

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