Document Detail

Association of estrogen receptor alpha and histone deacetylase 6 causes rapid deacetylation of tubulin in breast cancer cells.
MedLine Citation:
PMID:  19318565     Owner:  NLM     Status:  MEDLINE    
Estrogen receptor alpha (ERalpha) is a nuclear receptor that functions as a ligand-activated transcription factor. Besides its genomic action in nuclei, ERalpha could exert nongenomic actions at the plasma membrane. To investigate the mechanism underlying the nongenomic action of ERalpha in breast cancer cells, we generated a construct of membrane-targeted ERalpha (memER), an expression vector of ERalpha without the nuclear localizing signal and including instead the membrane-targeting sequence of Src kinase. MemER was stably expressed in human breast cancer MCF-7 cells. Cell migration test and tumorigenic assay in nude mice revealed that the in vitro motility and the in vivo proliferation activity of MCF-7 cells expressing memER were significantly enhanced compared with those of vector-transfected cells. Interestingly, the acetylation level of tubulin in memER-overexpressing cells was lower than that in control cells. We found that histone deacetylase (HDAC) 6 translocated to the plasma membrane shortly after estrogen stimulation, and rapid tubulin deacetylation subsequently occurred. We also showed that memER associated with HDAC6 in a ligand-dependent manner. Although tamoxifen is known for its antagonistic role in the ERalpha genomic action in MCF-7 cells, the agent showed an agonistic function in the memER-HDAC6 association and tubulin deacetylation. These findings suggest that ERalpha ligand dependently forms a complex with HDAC6 and tubulin at the plasma membrane. Estrogen-dependent tubulin deacetylation could provide new evidence for the nongenomic action of estrogen, which potentially contributes to the aggressiveness of ERalpha-positive breast cancer cells.
Kotaro Azuma; Tomohiko Urano; Kuniko Horie-Inoue; Shin-ichi Hayashi; Ryuichi Sakai; Yasuyoshi Ouchi; Satoshi Inoue
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-03-24
Journal Detail:
Title:  Cancer research     Volume:  69     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-02     Completed Date:  2009-06-02     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2935-40     Citation Subset:  IM    
Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
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MeSH Terms
Breast Neoplasms / metabolism*
COS Cells
Cell Line, Tumor
Cell Membrane / metabolism
Cell Movement / physiology
Cercopithecus aethiops
Estradiol / pharmacology
Estrogen Receptor alpha / metabolism*
Histone Deacetylases / metabolism*
Tubulin / metabolism*
Reg. No./Substance:
0/Estrogen Receptor alpha; 0/Tubulin; 50-28-2/Estradiol; EC protein, human; EC Deacetylases

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