Inhibition of canonical WNT signaling attenuates human leiomyoma cell growth
Identifieur interne : 001166 ( Main/Exploration ); précédent : 001165; suivant : 001167Inhibition of canonical WNT signaling attenuates human leiomyoma cell growth
Auteurs : Masanori Ono [États-Unis] ; Ping Yin [États-Unis] ; Antonia Navarro [États-Unis] ; Molly B. Moravek [États-Unis] ; John S. Coon V [États-Unis] ; Stacy A. Druschitz [États-Unis] ; Cara J. Gottardi [États-Unis] ; Serdar E. Bulun [États-Unis]Source :
- Fertility and Sterility [ 0015-0282 ] ; 2014.
Abstract
To assess the effect of three WNT/β-catenin pathway inhibitors—inhibitor of β-catenin and TCF4 (ICAT), niclosamide, and XAV939—on the proliferation of primary cultures of human uterine leiomyoma cells.
Prospective study of human leiomyoma cells obtained from myomectomy or hysterectomy.
University research laboratory.
Women (n = 38) aged 27–53 years undergoing surgery.
Adenoviral ICAT overexpression or treatment with varying concentrations of niclosamide or XAV939.
Cell proliferation, cell death, WNT/-catenin target gene expression or reporter gene regulation, β-catenin levels, and cellular localization.
Inhibitor of β-catenin and TCF4, niclosamide, or XAV939 inhibit WNT/β-catenin pathway activation and exert antiproliferative effects in primary cultures of human leiomyoma cells.
Three WNT/-catenin pathway inhibitors specifically block human leiomyoma growth and proliferation, suggesting that the canonical WNT pathway may be a potential therapeutic target for the treatment of uterine leiomyoma. Our findings provide rationale for further preclinical and clinical evaluation of ICAT, niclosamide, and XAV939 as candidate antitumor agents for uterine leiomyoma.
Url:
DOI: 10.1016/j.fertnstert.2014.01.017
PubMed: 24534281
PubMed Central: 4008647
Affiliations:
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Moravek</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Illinois</region></placeName><wicri:cityArea>Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago</wicri:cityArea></affiliation></author><author><name sortKey="Coon V, John S" sort="Coon V, John S" uniqKey="Coon V J" first="John S." last="Coon V">John S. Coon V</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Illinois</region></placeName><wicri:cityArea>Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago</wicri:cityArea></affiliation></author><author><name sortKey="Druschitz, Stacy A" sort="Druschitz, Stacy A" uniqKey="Druschitz S" first="Stacy A." last="Druschitz">Stacy A. Druschitz</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Illinois</region></placeName><wicri:cityArea>Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago</wicri:cityArea></affiliation></author><author><name sortKey="Gottardi, Cara J" sort="Gottardi, Cara J" uniqKey="Gottardi C" first="Cara J." last="Gottardi">Cara J. Gottardi</name><affiliation wicri:level="2"><nlm:aff id="aff2">Department of Medicine, Feinberg School of Medicine at Northwestern University, Chicago, Illinois</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Illinois</region></placeName><wicri:cityArea>Department of Medicine, Feinberg School of Medicine at Northwestern University, Chicago</wicri:cityArea></affiliation></author><author><name sortKey="Bulun, Serdar E" sort="Bulun, Serdar E" uniqKey="Bulun S" first="Serdar E." last="Bulun">Serdar E. Bulun</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Illinois</region></placeName><wicri:cityArea>Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago</wicri:cityArea></affiliation></author></analytic><series><title level="j">Fertility and Sterility</title><idno type="ISSN">0015-0282</idno><idno type="eISSN">1556-5653</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Objective</title><p>To assess the effect of three WNT/β-catenin pathway inhibitors—inhibitor of β-catenin and TCF4 (ICAT), niclosamide, and XAV939—on the proliferation of primary cultures of human uterine leiomyoma cells.</p></sec><sec><title>Design</title><p>Prospective study of human leiomyoma cells obtained from myomectomy or hysterectomy.</p></sec><sec><title>Setting</title><p>University research laboratory.</p></sec><sec><title>Patient(s)</title><p>Women (n = 38) aged 27–53 years undergoing surgery.</p></sec><sec><title>Intervention(s)</title><p>Adenoviral ICAT overexpression or treatment with varying concentrations of niclosamide or XAV939.</p></sec><sec><title>Main Outcome Measure(s)</title><p>Cell proliferation, cell death, WNT/-catenin target gene expression or reporter gene regulation, β-catenin levels, and cellular localization.</p></sec><sec><title>Result(s)</title><p>Inhibitor of β-catenin and TCF4, niclosamide, or XAV939 inhibit WNT/β-catenin pathway activation and exert antiproliferative effects in primary cultures of human leiomyoma cells.</p></sec><sec><title>Conclusion(s)</title><p>Three WNT/-catenin pathway inhibitors specifically block human leiomyoma growth and proliferation, suggesting that the canonical WNT pathway may be a potential therapeutic target for the treatment of uterine leiomyoma. 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Gottardi</name><name sortKey="Moravek, Molly B" sort="Moravek, Molly B" uniqKey="Moravek M" first="Molly B." last="Moravek">Molly B. Moravek</name><name sortKey="Navarro, Antonia" sort="Navarro, Antonia" uniqKey="Navarro A" first="Antonia" last="Navarro">Antonia Navarro</name><name sortKey="Yin, Ping" sort="Yin, Ping" uniqKey="Yin P" first="Ping" last="Yin">Ping Yin</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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