Document Detail


Estrogen prevents senescence through induction of WRN, Werner syndrome protein.
MedLine Citation:
PMID:  20395656     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Werner syndrome is a well-known human progeria. It has been revealed that loss of human WRN is a causal factor of this disease. Since pathological features of Werner syndrome resemble those of menopausal women and become apparent during puberty, we examined the effect of estrogen on WRN gene expression. Here, we reveal that WRN is induced by estrogen but not testosterone. Treatment with estrogen can induce WRN expression at the transcription and translation level in a human breast cell line. Forced expression of the estrogen receptor can restore the responsiveness of WRN to estrogen in a non-responsive cell line. Treatment with estrogen can block DNA damage-induced senescence. Moreover, WRN is suppressed by ATR that is activated by DNA damage, whereas WRN can be induced by ATR elimination. Our results suggest that WRN is essential for prevention of senescence. In addition, our results imply that the reduction of WRN in menopause could be an important factor for menopausal syndrome.
Authors:
Su-Jin Lee; Sun-Hye Lee; Nam-Chul Ha; Bum-Joon Park
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-15
Journal Detail:
Title:  Hormone research in pædiatrics     Volume:  74     ISSN:  1663-2826     ISO Abbreviation:  Horm Res Paediatr     Publication Date:  2010  
Date Detail:
Created Date:  2010-07-19     Completed Date:  2010-11-15     Revised Date:  2011-03-22    
Medline Journal Info:
Nlm Unique ID:  101525157     Medline TA:  Horm Res Paediatr     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  33-40     Citation Subset:  IM    
Copyright Information:
Copyright 2010 S. Karger AG, Basel.
Affiliation:
Department of Molecular Biology, College of Natural Science, Pusan National University, Busan, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
Blotting, Western
Cell Aging / drug effects*,  genetics,  physiology
Cell Cycle Proteins / metabolism
Cell Line, Tumor
Child
DNA Damage
Estrogen Receptor alpha / genetics,  metabolism*
Estrogens / pharmacology*
Exodeoxyribonucleases / biosynthesis*,  genetics
Female
Gene Expression Regulation / drug effects
HCT116 Cells
Humans
Immunohistochemistry
Protein-Serine-Threonine Kinases / metabolism
RNA, Messenger / biosynthesis,  genetics
RecQ Helicases / biosynthesis*,  genetics
Reverse Transcriptase Polymerase Chain Reaction
Testosterone / pharmacology
Transcription, Genetic / drug effects
Werner Syndrome / drug therapy,  genetics,  metabolism*,  pathology*
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Estrogen Receptor alpha; 0/Estrogens; 0/RNA, Messenger; 58-22-0/Testosterone; EC 2.7.1.-/ATR protein, human; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 3.1.-/Exodeoxyribonucleases; EC 3.6.1.-/RecQ Helicases; EC 3.6.1.-/WRN protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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