Functional characterization of seven single-nucleotide polymorphisms of the steroid sulfatase gene found in a Japanese population

Jun Matsumoto, Noritaka Ariyoshi, Itsuko Ishii, Mitsukazu Kitada

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)267-272
Number of pages6
JournalJournal of Human Genetics
Volume58
Issue number5
DOIs
Publication statusPublished - May 2013
Externally publishedYes

Fingerprint

Steryl-Sulfatase
Single Nucleotide Polymorphism
Dehydroepiandrosterone Sulfate
Population
Genes
Enzymes
Steroids
5' Flanking Region
5' Untranslated Regions
COS Cells
MCF-7 Cells
Reporter Genes
Codon
Placenta
Sulfates
Healthy Volunteers
Hormones
Breast Neoplasms
Proteins

Keywords

  • breast cancer
  • dehydroepiandrosterone sulfate
  • estrone sulfate
  • Japanese
  • SNP
  • steroid sulfatase
  • STS
  • STS inhibitor

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Functional characterization of seven single-nucleotide polymorphisms of the steroid sulfatase gene found in a Japanese population. / Matsumoto, Jun; Ariyoshi, Noritaka; Ishii, Itsuko; Kitada, Mitsukazu.

In: Journal of Human Genetics, Vol. 58, No. 5, 05.2013, p. 267-272.

Research output: Contribution to journalArticle

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