Abstract:
:Triple-negative breast cancers lack estrogen receptor α (ERα), progesterone receptor, and do not overexpress human epidermal growth factor receptor 2 (Her-2). They are neither susceptible to endocrine therapy nor to a therapy using the anti-Her-2 antibody, trastuzumab. Therefore, an efficient targeted therapy is warranted. Triple-negative breast tumors frequently express membrane bound estrogen receptor G-protein coupled receptor (GPR30). As proof of principle, we analyzed the consequences of a knock-down of GPR30 expression on the growth regulation of triple-negative breast cancer cell lines. Cells of triple-negative breast cancer cell lines were transfected with siRNA against GPR30 or control siRNA, and cell growth was stimulated either with 10(⁻⁹) M 17β-estradiol or 10(⁻⁶) M 4-hydroxytamoxifen. Cell proliferation was measured using Alamar blue staining. Activation of c-Src and epidermal growth factor (EGF)-receptor was assessed using western blot. Expression of c-fos was quantified by reverse transcription polymerase chain reaction. Seven days after transfection with siRNA, GPR30 mRNA in triple-negative breast cancer cell lines MDA-MB-435 and HCC1806 was reduced by 74 and 90%, respectively. 10(⁻⁸) M 17β-estradiol enhanced proliferation of MDA-MB-435 to 129.6±5.4% of control (p<0.05) and HCC1806 to 156.9±15.4% of control (p<0.05), respectively. 10(⁻⁶) M 4-hydroxytamoxifen increased cell number of MDA-MB-435 to 121.0±6.9% of control (p<0.05) and HCC1806 to 124.5±12.1% of control (n.s.), respectively. This increased proliferation by the two estrogenic compounds was completely prevented by knock-down of GPR30 expression in both cell lines. In control cells, activity of Src kinase was increased 3-fold by estradiol and 3.8-fold using 4-hydroxytamoxifen. Transactivation of the EGF-receptor was similarly increased in both cell lines by 17β-estradiol and 4-hydroxytamoxifen. Both compounds increased c-fos expression 1.5- and 3.1-fold, respectively. Knock-down of GPR30 expression completely abolished activation of all these signaling pathways responsible for enhanced proliferation. A pharmacological inhibition of GPR30 by specific small molecular inhibitors might prove to be an appropriate targeted therapy of triple-negative breast cancer in the future.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Girgert R,Emons G,Gründker Cdoi
10.1007/s10549-012-1968-xsubject
Has Abstractpub_date
2012-07-01 00:00:00pages
199-205issue
1eissn
0167-6806issn
1573-7217journal_volume
134pub_type
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/B:BREA.0000041622.30169.16
更新日期:2004-09-01 00:00:00
abstract:PURPOSE:Estrogen exposure is involved in both breast cancer susceptibility and the prognosis in patients with breast cancer. Aromatase is involved in the production of estrogens, and altered expression of it might be associated with the prognosis. The aim of this study was to examine the effect of single nucleotide pol...
journal_title:Breast cancer research and treatment
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doi:10.1007/s10549-007-9822-2
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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
doi:10.1007/s10549-006-9224-x
更新日期:2006-11-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-017-4384-4
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-015-3427-y
更新日期:2015-06-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-017-4400-8
更新日期:2017-11-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-010-1325-x
更新日期:2011-02-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-007-9631-7
更新日期:2008-05-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/BF00682736
更新日期:1994-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01811240
更新日期:1988-12-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1006170811237
更新日期:1999-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-06075-6
更新日期:2021-01-13 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-017-4413-3
更新日期:2017-11-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF00666043
更新日期:1995-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2491-4
更新日期:2013-04-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-017-4183-y
更新日期:2017-06-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章,meta分析
doi:10.1007/s10549-008-0195-y
更新日期:2009-08-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF00662134
更新日期:1993-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1006394401199
更新日期:2000-03-01 00:00:00
abstract::Although a significant proportion of familial aggregation of breast cancer remains unexplained, many of the currently known breast cancer susceptibility genes, including BRCA1, BRCA2 and TP53, play a role in maintaining genome integrity by engaging in DNA repair. RAD51L1 is one of the five RAD51 paralogs involved in h...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-011-1539-6
更新日期:2011-08-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-017-4615-8
更新日期:2018-04-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/s10549-020-05810-3
更新日期:2020-10-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-011-1734-5
更新日期:2012-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-018-05112-9
更新日期:2019-08-01 00:00:00
abstract::Epidermal growth factor receptor (EGFr) levels were analyzed in 140 primary breast cancer specimens by immunohistochemical assay (ICA), competitive binding assay (BA), or enzyme immunoassay (EIA). Thirty-nine of 118 specimens (33.1%) were scored as positive by ICA, 30 of 116 (25.9%; cut-off level 10 fmol/mg protein) b...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF00666582
更新日期:1993-12-01 00:00:00
abstract::The clinical and pathological heterogeneity of breast cancer has instigated efforts to stratify breast cancer sub-types according to molecular profiles. These profiling efforts are now being augmented by large-scale functional screening of breast tumour cell lines, using approaches such as RNA interference. We have de...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-010-0945-5
更新日期:2010-11-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-008-9948-x
更新日期:2009-02-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/s10549-017-4419-x
更新日期:2017-11-01 00:00:00
abstract::The tumor-stroma ratio has previously been shown to be prognostic for patients with invasive breast cancer. We present a validation study to assess the prognostic significance in lymph node-negative, premenopausal patients from the perioperative chemotherapy trial (POP trial, 10854) conducted by the European Organizat...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2571-5
更新日期:2013-06-01 00:00:00