Document Detail


Stable inhibition of specific estrogen receptor α (ERα) phosphorylation confers increased growth, migration/invasion, and disruption of estradiol signaling in MCF-7 breast cancer cells.
MedLine Citation:
PMID:  22733972     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Elevated phosphorylation of estrogen receptor α (ERα) at serines 118 (S118) and 167 (S167) is associated with favorable outcome for tamoxifen adjuvant therapy and may serve as surrogate markers for a functional ERα signaling pathway in breast cancer. It is possible that loss of phosphorylation at S118 and/or S167 could disrupt ERα signaling, resulting in aggressive ERα-independent breast cancer cells. To this end, MCF-7 breast cancer cells were stably transfected with an ERα-specific short hairpin RNA that reduced endogenous ERα. The resulting cell line was stably transfected with wild-type ERα (ER-AB cells), or ERα containing serine to alanine mutation at S118 or S167 (S118A cells and S167A cells, respectively). These stable cell lines expressed approximately equivalent ERα compared with parental MCF-7 cells and were evaluated for growth, morphology, migration/invasion, and ERα-regulated gene expression. S118A cells and S167A cells exhibited increased growth and migration/invasion in vitro. Forward- and side-scatter flow cytometry revealed that S167A cells were smaller in size, and both S118A and S167A cells exhibited less cellular complexity. S118A and S167A cells expressed pancytokeratin and membrane localization of β-catenin and did not express vimentin, indicating retention of epithelial lineage markers. Expression of ERα-target genes and other genes regulated by ERα signaling or involved in breast cancer were markedly altered in both S118A and S167A cells. In summary, attenuated phosphorylation of ERα at S118 and S167 significantly affected cellular physiology and behavior in MCF-7 breast cancer cells, resulting in increased growth, migration/invasion, compromised expression of ERα target genes, and markedly altered gene expression patterns.
Authors:
B P Huderson; T T Duplessis; C C Williams; H C Seger; C G Marsden; K J Pouey; S M Hill; B G Rowan
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-06-25
Journal Detail:
Title:  Endocrinology     Volume:  153     ISSN:  1945-7170     ISO Abbreviation:  Endocrinology     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-08-24     Completed Date:  2012-10-29     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4144-59     Citation Subset:  AIM; IM    
Affiliation:
Tulane University School of Medicine, Department of Structural and Cellular Biology, 1430 Tulane Avenue SL-49, New Orleans, Louisiana 70112, USA.
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MeSH Terms
Descriptor/Qualifier:
Breast Neoplasms / metabolism*
Cell Line, Tumor
Cell Movement / genetics,  physiology
Cell Proliferation
Estrogen Receptor alpha / genetics,  metabolism*
Female
Gene Expression Regulation, Neoplastic / genetics
Humans
Phosphorylation
RNA, Small Interfering
Signal Transduction / genetics,  physiology
Grant Support
ID/Acronym/Agency:
R01DK06832/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Estrogen Receptor alpha; 0/RNA, Small Interfering
Comments/Corrections

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


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