Abstract:
:Estrogen receptor-alpha (ERα)-positive breast cancer is often treated with antihormonal regimens. However, resistance to treatment is common, leading to metastatic disease. ERα activity requires the functional involvement of pioneer factors FOXA1 and GATA3, which enable ERα-chromatin binding and are crucial for ERα-driven cell proliferation. FOXA1 was found increased in metastatic breast cancers in relation to the primary tumor, but a comprehensive clinical assessment thereof, in relation to different metastatic sites and endocrine therapy usage, is currently lacking. Prior cell line-based reports, however, have revealed that FOXA1 is required for tamoxifen-resistant tumor cell proliferation. We studied expression levels of ERα, GATA3, and FOXA1 by immunohistochemistry in samples from both primary tumors and various metastatic sites. For all factors, expression levels varied between the metastatic sites. For pleural metastases, strong variation was found in FOXA1 and GATA3 levels. Although GATA3 levels remained unaltered between primary breast cancer and pleural metastases, FOXA1 levels were reduced exclusively in metastases of patients who received endocrine therapies in the adjuvant setting, even though ERα was still expressed. Importantly, decreased FOXA1 levels in pleural metastases correlated with hormone irresponsiveness in the palliative setting, while no such correlation was found for GATA3. With this, we show divergent clinical correlations of the two ERα pioneer factors FOXA1 and GATA3 in metastatic breast cancer, where endocrine therapy resistance was associated with decreased FOXA1 levels in pleural metastases.
journal_name
Mol Oncoljournal_title
Molecular oncologyauthors
Schrijver W,Schuurman K,van Rossum A,Droog M,Jeronimo C,Salta S,Henrique R,Wesseling J,Moelans C,Linn SC,van den Heuvel M,van Diest P,Zwart Wdoi
10.1002/1878-0261.12353subject
Has Abstractpub_date
2018-11-01 00:00:00pages
1884-1894issue
11eissn
1574-7891issn
1878-0261journal_volume
12pub_type
临床试验,杂志文章,多中心研究abstract::Cancer is a multifactorial and heterogeneous disease. The corresponding complexity appears at multiple levels: from the molecular and the cellular constitution to the macroscopic phenotype, and at the diagnostic and therapeutic management stages. The overall complexity can be approximated to a certain extent, e.g. cha...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
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abstract::In breast cancer (BC), the presence of cancer stem cells (CSCs) has been related to relapse, metastasis, and radioresistance. Radiotherapy (RT) is an extended BC treatment, but is not always effective. CSCs have several mechanisms of radioresistance in place, and some miRNAs are involved in the cellular response to io...
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journal_title:Molecular oncology
pub_type: 杂志文章
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journal_title:Molecular oncology
pub_type: 杂志文章
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journal_title:Molecular oncology
pub_type: 杂志文章
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journal_title:Molecular oncology
pub_type: 杂志文章,评审
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pub_type: 杂志文章
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journal_title:Molecular oncology
pub_type:
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journal_title:Molecular oncology
pub_type: 杂志文章,评审
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12521
更新日期:2019-08-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2013.02.017
更新日期:2013-06-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.04.006
更新日期:2015-08-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12110
更新日期:2017-10-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12053
更新日期:2017-05-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
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更新日期:2014-05-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12368
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pub_type: 杂志文章
doi:10.1002/1878-0261.12748
更新日期:2020-08-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章,评审
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更新日期:2010-06-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章,评审
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更新日期:2017-07-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章,评审
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更新日期:2015-05-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12536
更新日期:2019-09-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.molonc.2015.09.006
更新日期:2016-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1002/1878-0261.12790
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journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2014.03.010
更新日期:2014-06-01 00:00:00