Steroid sulfatase and estrogen sulfotransferase in human prostate cancer

Nakamura, Yasuhiro; Suzuki, Takashi; Fukuda, Tsuyoshi; Itoh, Akihiro; Endo, Mareyuki; Moriya, Takuya; Arai, Yoichi; Sasano, Hironobu

doi:10.1002/pros.20426

Cited by 54 publications

(54 citation statements)

References 19 publications

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“…It was reported that DHEAS is hydrolyzed by STS in LNCaP cells [27] and the expression of STS is increased in prostate cancer cells, compared to non-malignant prostate tissues, as determined by immunohistochemical staining [28]. In the present study, expression of STS mRNA was detected in LNCaP cells, and this expression was not affected under androgen-depleted conditions ( Figure 1C).…”

Section: Contribution Of Oatp1a2 To Dheas-induced Cell Growth In Lncasupporting

confidence: 63%

Enhanced expression of organic anion transporting polypeptides (OATPs) in androgen receptor-positive prostate cancer cells: Possible role of OATP1A2 in adaptive cell growth under androgen-depleted conditions

Arakawa

Nakanishi

Yanagihara

et al. 2012

Biochemical Pharmacology

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The biological mechanisms underlying castration resistance of prostate cancer are not fully understood. In the present study, we examined the role of organic anion transporting polypeptides (OATPs) as importers of dehydroepiandrosterone sulfate (DHEAS) into cells to support growth under androgen-depleted conditions. Cell growth and mRNA expression of OATP genes were studied in human prostate cancer LNCaP and 22Rv1 cells under androgen-depleted conditions. The stimulatory effect of DHEAS on cell growth was investigated in LNCaP cells in which OATP1A2 had been silenced. Growth of both cell lines was stimulated by DHEAS and the effect was attenuated by STX64, an inhibitor of steroid sulfatase which can covert DHEAS to DHEA. OATP1A2 mRNA expression was increased most prominently among various genes tested in LNCaP cells grown in androgen-depleted medium. Similar results were obtained with 22Rv1 cells. Furthermore, the characteristics of

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Section: Contribution Of Oatp1a2 To Dheas-induced Cell Growth In Lncasupporting

confidence: 63%

Enhanced expression of organic anion transporting polypeptides (OATPs) in androgen receptor-positive prostate cancer cells: Possible role of OATP1A2 in adaptive cell growth under androgen-depleted conditions

Arakawa

Nakanishi

Yanagihara

et al. 2012

Biochemical Pharmacology

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“…These targets include tissues of the reproductive system, such as the mammary gland and uterus, cells in the hypothalamus and pituitary, bone, and liver, as well as the cardiovascular system, where estrogens exert cardioprotective effects [35]. In addition to stimulating normal mammary gland growth and duct development, pathological levels of estrogens increase proliferation and metastatic activity of breast cancer cells and stimulate proliferation of uterine cells [36,37]. While much is known about the physiology of estrogens, little has been documented about the oxidative regulation of SULTs.…”

Section: Discussionmentioning

confidence: 99%

“…Redox regulation of hSULT1E1 changes bioactive E 2 levels in vivo. This in turn is related to E 2 -dependent tumorigenesis in the breast, endometrium, and prostate [36,37]. Human liver cytosol (final concentration, 1.0 mg/ml) or purified hSULT1E1 (final concentration, 0.1 mg/ml) were incubated in Tris buffer (pH 6.2) at room temperature with various GSSG concentrations and durations, as indicated.…”

Section: Discussionmentioning

confidence: 99%

Redox regulation of human estrogen sulfotransferase (hSULT1E1)

Maiti¹,

Zhang²,

Chen³

2007

Biochemical Pharmacology

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Sulfotransferases (SULTs) are enzymes that catalyze the sulfation of hydroxyl-containing compounds. Sulfation regulates hormone activities and detoxifies xenobiotics. Human estrogen sulfotransferase (hSULT1E1) catalyzes the sulfation of estrogens and regulates estrogen bioactivities. Oxidative regulation provides a biological mechanism for regulating enzyme activities in vivo. The oxidative regulation of human SULTs has not been reported. In this study, we used amino acid modification, manipulation of intracellular redox state, and site-directed mutagenesis to study the redox regulation of human SULTs and specifically the mechanism of hSULT1E1 inhibitory regulation by oxidized glutathione (GSSG). Of the four major human SULTs, hSULT1A1, hSULT1A3, and hSULT2A1 do not undergo redox regulation; hSULT1E1, on the other hand, can be redox regulated. GSSG inactivated hSULT1E1 activity in an efficient, time-and concentrationdependant manner. The co-enzyme adenosine 3′-phosphate 5′-phosphosulfate protected hSULT1E1 from GSSG-associated inactivation. A reduced glutathione (GSH) inducer (N-acetyl cysteine) significantly increased while a GSH depletor (buthionine sulfoxamine) significantly decreased hSULT1E1 activity, but both failed to affect the amount of hSULT1E1 protein in human hepatocyte carcinoma Hep G2 cells. Crystal structure suggested that no Cys residues exist near the active sites of hSULT1A1, hSULT1A3, and hSULT2A1, but Cys residues do exist within the active site of hSULT1E1. Site-directed mutagenesis demonstrated that Cys83 is critical for the redox regulation of hSULT1E1. This first report on the redox regulation of human SULTs suggests that the redox regulation of hSULT1E1 may interrupt the regulation and function of estrogens under various physiological and pathological conditions.

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“…STS has been shown to be expressed in normal human prostate tissue (Reed et al 2005), prostate cancer cell lines LNCaP, DU-145 and PC3 (Nakamura et al 2006) and in primary prostate homogenates (Klein et al 1989). Furthermore, one study found that STS is expressed in the majority of localised prostate cancers showing higher expression in malignant tissues compared with benign (Nakamura et al 2006). The activity of STS has been proven within the human prostate for the desulphation of dehydroepiandrosterone sulphate (DHEAS) into DHEA, an androgen precursor (Farnsworth 1973).…”

Section: :6mentioning

confidence: 99%

“…The activity of STS has been proven within the human prostate for the desulphation of dehydroepiandrosterone sulphate (DHEAS) into DHEA, an androgen precursor (Farnsworth 1973). Moreover, E 1 synthesis from desulphation of E 1 S within the prostate is putatively 10-fold greater than synthesis via aromatase (Nakamura et al 2006). The relevance of STS in cancer has been more extensively studied in breast cancer, where there is significantly higher expression of STS than in normal breast (Utsumi et al 2000).…”

Section: :6mentioning

confidence: 99%

In touch with your feminine side: how oestrogen metabolism impacts prostate cancer

Rahman

Hofland

Foster

2016

Endocrine-Related Cancer

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Prostate cancer is the primary cancer in males, with increasing global incidence rates making this malignancy a significant healthcare burden. Androgens not only promote normal prostate maturity but also influence the development and progression of prostate cancer. Intriguingly, evidence now suggests endogenous and exogenous oestrogens, in the form of phytoestrogens, may be equally as relevant as androgens in prostate cancer growth. The prostate gland has the molecular mechanisms, catalysed by steroid sulphatase (STS), to unconjugate and utilise circulating oestrogens. Furthermore, prostate tissue also expresses enzymes essential for local oestrogen metabolism, including aromatase (CYP19A1) and 3β- and 17β-hydroxysteroid dehydrogenases. Increased expression of these enzymes in malignant prostate tissue compared with normal prostate indicates that oestrogen synthesis is favoured in malignancy and thus may influence tumour progression. In contrast to previous reviews, here we comprehensively explore the epidemiological and scientific evidence on how oestrogens impact prostate cancer, particularly focusing on pre-receptor oestrogen metabolism and subsequent molecular action. We analyse how molecular mechanisms and metabolic pathways involved in androgen and oestrogen synthesis intertwine to alter prostate tissue. Furthermore, we speculate on whether oestrogen receptor status in the prostate affects progression of this malignancy.

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Steroid sulfatase and estrogen sulfotransferase in human prostate cancer

Abstract: STS and EST are expressed and may be involved in local production and metabolism of estrogens in human prostate cancers.

Cited by 54 publications

References 19 publications

Enhanced expression of organic anion transporting polypeptides (OATPs) in androgen receptor-positive prostate cancer cells: Possible role of OATP1A2 in adaptive cell growth under androgen-depleted conditions

Enhanced expression of organic anion transporting polypeptides (OATPs) in androgen receptor-positive prostate cancer cells: Possible role of OATP1A2 in adaptive cell growth under androgen-depleted conditions

Redox regulation of human estrogen sulfotransferase (hSULT1E1)

In touch with your feminine side: how oestrogen metabolism impacts prostate cancer

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