Abstract:
:Estrogen and selective estrogen receptor modulators (SERMs) differentially impact endometrial cell function, however, the biological basis of these differences is not established. Deregulated cell adhesion to the extracellular matrix, cell movement and invasion are related to endometrial disorders, such as endometriosis or endometrial cancer. Remodeling of the actin cytoskeleton is required to achieve cell adhesion and movement. Estrogen receptor (ER) regulates actin and cell membrane remodeling through extra-nuclear signaling cascades. In this article, we show that administration of 17beta-estradiol (E2) and tamoxifen (TAM) to immortalized Ishikawa endometrial cells or to human endometrial stromal cells (ESC) results in remodeling of actin fibers and cell membrane. This is linked to rapid phosphorylation on Thr(558) of the actin-binding protein moesin and enhanced migration and invasion of normal and Ishikawa cells. Raloxifene (RAL) does not result in moesin activation or actin remodeling. When endometrial cells are exposed to E2 in the presence of TAM or RAL, both SERMs interfere with the recruitment of moesin, with the remodeling of the cytoskeleton, and with cell movement and migration induced by E2. The differential actions of E2, TAM and RAL are linked to a distinct modulation of the extra-nuclear signaling of ER to G proteins and to the Rho-associated kinase. These findings increase our understanding of the actions of estrogen and SERMs in endometrial cells and highlight potential molecular targets to interfere with the estrogen-related altered cell adhesion encountered in endometrial disorders.
journal_name
Mol Hum Reprodjournal_title
Molecular human reproductionauthors
Flamini MI,Sanchez AM,Goglia L,Tosi V,Genazzani AR,Simoncini Tdoi
10.1093/molehr/gap045subject
Has Abstractpub_date
2009-10-01 00:00:00pages
675-85issue
10eissn
1360-9947issn
1460-2407pii
gap045journal_volume
15pub_type
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journal_title:Molecular human reproduction
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更新日期:2006-03-01 00:00:00
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更新日期:2003-02-01 00:00:00
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更新日期:1997-09-01 00:00:00
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更新日期:2011-02-01 00:00:00
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更新日期:2011-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2017-07-01 00:00:00
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更新日期:2008-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:1998-12-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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