title: Functional characterization of seven single-nucleotide polymorphisms of the steroid sulfatase gene found in a Japanese population.
abstract: Steroid sulfatase (STS) is an enzyme that hydrolyzes steroid sulfates such as dehydroepiandrosterone sulfate (DHEA-S) and estrone sulfate. STS has a key role in the synthesis of steroid hormones in placenta and breast cancer cells. Recently, we have identified six novel single-nucleotide polymorphisms (SNPs) and one nonsynonymous SNP (V476M) in the STS gene in a Japanese population. To clarify the effects of SNPs in the 5'-flanking region or 5' untranslated region on transcriptional activity, a reporter gene assay was conducted. In addition, DHEA-S desulfatase activity of a variant (Met at codon 476)-type enzyme was compared with that of the wild (Wd)-type enzyme in COS-1 cells. The transcriptional activities were significantly decreased (155A) and increased (-2837A and -1588C) in MCF-7 cells. On the other hand, no significant difference was found in expression levels of STS protein or specific activities of DHEA-S desulfation between Wd and the variant enzymes. This is the first report on the effects of various SNPs in the STS gene detected in Japanese healthy subjects.
authors: Department of Clinical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
authors: Jun
authors: J
authors: Matsumoto
authors: Noritaka
authors: N
authors: Ariyoshi
authors: Itsuko
authors: I
authors: Ishii
authors: Mitsukazu
authors: M
authors: Kitada
mesh_terms: D024506:5' Flanking Region; D000818:Animals; D044466:Asian People / Q000235:genetics*; D019556:COS Cells; D002384:Catalysis; D002522:Chlorocebus aethiops; D004789:Enzyme Activation; D015870:Gene Expression; D005786:Gene Expression Regulation; D023061:Gene Order; D006801:Humans; D007564:Japan; D061986:MCF-7 Cells; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics; D043266:Steryl-Sulfatase / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D012333:RNA, Messenger; C584039:STS protein, human; D043266:Steryl-Sulfatase