PAPSS1 might be important for growth of estrogen-sensitive breast cancer cells as a recent study revealed that overexpression of SULT1E1 and PAPSS1 resulted in growth inhibition [21]. 2. selleck products steroid Sulfatase (STS) The steroid sulfatase (STS) belongs to the family of arylsulfatases in the

sulfatase superfamily, whose members catalyze the hydrolysis of sulfate ester bonds in various endogenous and exogenous substrates. STS is also known as arylsulfatase C, and in contrast to the cytosolic expression of arylsulfatases A and B, this enzyme is located in the endoplasmic reticulum of various tissues [23]. STS has a central role in the formation of active sex steroid hormones, Inhibitors,research,lifescience,medical as it hydrolyzes several steroid sulfates, including E1S and DHEA-S to E1 and DHEA, respectively [17]. The human STS gene is localized on the X-chromosome and consists of 10 exons. Inactivating mutations in STS gene have been associated with X-linked ichthyosis. Six different promoters were detected to drive STS expression giving rise to transcripts with unique Inhibitors,research,lifescience,medical first exons, and exon 1 alpha was associated with the promoter that drives expression in the placenta [24]. Induction of STS transcription by estradiol through binding to ER and via activation of estrogen-response elements in

the promoter region results in driving the 1a and 1b transcripts Inhibitors,research,lifescience,medical in breast carcinoma [25]. Furthermore, regulation of STS activity by tumor necrosis factor alpha and interleukin 6 was Inhibitors,research,lifescience,medical found in breast cancer, most likely through a posttranslational modification [26]. 3. Estrogen Sulfotransferase (SULT1E1) Cytosolic sulfotransferases transfer sulfate from active sulfate (5′phosphadenosine-3′-phosphosulfate) to nucleophilic groups of their substrates. Belonging to the group of Phase 2 detoxification enzymes, they catalyze the biotransformation of hydroxysteroid Inhibitors,research,lifescience,medical and thyroid hormones, phenols,

arylamines, and primary alcohols. Four SULT families have been identified, namely, the phenol-metabolizing SULT1, the hydroxysteroid sulfating SULT2, and the SULT family 4 and 6 [18]. The two latter families are poorly characterized for c-Met inhibitor review their substrate specificity and tissue distribution. At least six SULT isoforms catalyze the sulfate conjugation of E2, but only two, namely, SULT1E1 and SULT2A1 mediate the sulfonation of estrone (E1). SULT1E1 is considered as the “estrogen sulfotransferase,” as it has the highest affinity for E2 and E1 from all SULTs. It is the only SULT that displays an affinity for E1, E2, and various synthetic estrogens in a physiological concentration range (in the nanomolar range) [26]. Deletion of SULT1E1 genes results in reproductive abnormalities involving both male and female animals [27]. In the liver, the pregnane X receptor was found to represses the SULT1E1 gene, which may block inactivation of estrogens [28]. The SULT1E1 gene is located on chromosome 4q3.