Abstract:
:Estrogen receptor alpha (ERalpha) is a well-known target for signaling pathways originating from growth factor receptors. Reactive oxygen species (ROS) can induce activation of extracellular response kinase 1/2 (Erk1/2) and protein kinase B (Akt). Both kinases have been implicated in the phosphorylation of serine 118 and serine 167 on ERalpha, respectively. This activity may lead either to ligand-independent activation of ERalpha or down-regulation of ERalpha and may contribute to development of the resistance to endocrine therapy. Treatment of MCF-7 human breast cancer cells with glucose oxidase (GO, 0.1 un/ml) induced transient phosphorylation of serine 118 and serine 167. The increase in expression of p-ser118-ERalpha was 355 +/- 98% (mean +/- SD) and of p-ser167-ERalpha was 632 +/- 355%. These effects were enhanced in Her2 over-expressing MCF7 cells. ERalpha expression declined to 63 +/- 20% within the first 90 min of treatment and was below 10% 24 h later. ROS induced phosphorylation of ERalpha resulted in decreased expression of pS2 and progesterone receptor. Activation of Erk1/2 and Akt was transient with highest levels of Erk1/2 being 595 +/- 143% and p-Akt 311 +/- 125%. Inhibition of Erk1/2 by U0126 (10 microM) decreased p-ser118-ERalpha by 51.7 +/- 8.5% and decreased p-ser167-ERalpha by 41.9 +/- 16.9% whereas inhibition of Akt by LY294002 (20 microM) and wortmannin (500 nM) or by siRNA knock-down, had no effect on p-ser167-ERalpha expression. Our data show for the first time that ROS can induce post-translational modifications of ERalpha at serine 118 and serine 167, and may lead to ERalpha down-regulation in human breast cancer cells. Both the phosphorylation and consequent down-regulation of ERalpha may be a mechanism associated with development of endocrine therapy resistance.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Weitsman GE,Weebadda W,Ung K,Murphy LCdoi
10.1007/s10549-008-0221-0subject
Has Abstractpub_date
2009-11-01 00:00:00pages
269-79issue
2eissn
0167-6806issn
1573-7217journal_volume
118pub_type
杂志文章abstract::After more than 100 reported randomized trials of systemic adjuvant therapy in breast cancer, it is clear that this therapy will prolong the time to recurrence and the survival time significantly, at least in some patient subsets. But there is less than complete agreement as to which subsets, which therapies, how much...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,随机对照试验,评审
doi:10.1007/BF01805971
更新日期:1989-10-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章
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journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Breast cancer research and treatment
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
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journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
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更新日期:2017-02-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
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journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章
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更新日期:2012-12-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-05543-3
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-019-05429-z
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
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journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1992-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
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更新日期:1997-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-06054-x
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-015-3636-4
更新日期:2015-12-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
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更新日期:2000-09-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章,多中心研究
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pub_type: 杂志文章
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更新日期:2017-09-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
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更新日期:2016-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2011-01-01 00:00:00
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journal_title:Breast cancer research and treatment
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更新日期:2014-07-01 00:00:00