title: WISP-2 is a secreted protein and can be a marker of estrogen exposure in MCF-7 cells.
abstract: As many structurally diverse chemicals have been reported to function as estrogens, evaluations for estrogenicity of compounds are of widespread concern. Recently, we identified WISP-2 (Wnt-1 inducible signaling pathway protein 2) as a novel estrogen-inducible gene in human breast cancer cells. In this study, we examined whether WISP-2 could be utilized as a marker for screening environmentally relevant compounds for estrogenicity. In MCF-7 cells, progesterone, dexamethasone, tri-iodothyronine, and 2,3,7,8-tetrachlorodibenzo-p-dioxin did not regulate the expression of WISP-2, indicating that its induction is highly specific for hormones that interact with the estrogen receptor. Western blot analysis detected WISP-2 protein induced by 17-beta-estradiol (E2), not only in the cell lysates but also in the culture supernatant of exposed cells, indicating that WISP-2 was a secreted protein. The induction of WISP-2 protein by E2 in the culture supernatant was dose-dependent with estimated EC(50) levels between 10 and 100 pM. Our results demonstrated the capacity to screen environmental compounds for estrogenicity via WISP-2 induction.
authors.affiliation: Environmental Science Center, University of Tokyo, 7-3-1, Hongo, Bunkyoku, Tokyo 113-0033, Japan. inadera@esc.u-tokyo.ac.jp
authors.forename: Hidekuni
authors.initials: H
authors.lastname: Inadera
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Dong
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
mesh_terms: D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D055511:CCN Intercellular Signaling Proteins; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen / Q000378:metabolism*; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D055511:CCN Intercellular Signaling Proteins; C413323:CCN5 protein, human; D004967:Estrogens; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D012097:Repressor Proteins; D014157:Transcription Factors