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Inhibition of Estrogen Signaling Reduces the Incidence of BRCA1-associated Mammary Tumor Formation
Baek H.J.2; Kim S.E.2; Choi E.K.2; Kim J.K.2; Shin D.H.2; Park E.J.2; Kim T.H.2; Kim J.-Y.2; Kim K.G.1; Deng C.-X.3; Kim S.S.2
2018
Source PublicationInternational journal of biological sciences
ISSN14492288
Volume14Issue:12Pages:1755-1768
Abstract

BRCA1-deficient breast cancer is a very well-known hereditary cancer. However, except for resection of normal mammary glands and ovaries, there is no acceptable measure for proactively preventing tumor development. Importantly, inherited BRCA1 mutations are closely associated with tumors in hormone-responsive tissues. Here, we examined the effects of estrogen on the accumulation of genetic instabilities upon loss of BRCA1, and assessed the contribution of estrogen signaling to the incidence and progression of Brca1-mutated mammary tumors. Our in vitro studies showed that treatment of BRCA1-depleted breast cancer cells with estrogen induced proliferation. Additionally, estrogen reduced the ability of these BRCA1-knockdown cells to sense radiation-induced DNA damage and also facilitated G1/S progression. Moreover, long-term treatment of Brca1-mutant (Brca1co/coMMTV-Cre) mice with the selective estrogen receptor (ER)-α degrader, fulvestrant, decreased the tumor formation rate from 64% to 36%, and also significantly reduced mammary gland density in non-tumor-bearing mice. However, in vivo experiments showed that fulvestrant treatment did not alter the progression of ER-positive Brca1-mutant tumors, which were frequently identified in the aged population and showed less aggressive tendencies. These findings enhance our understanding of how ER-α signaling contributes to BRCA1-deficient mammary tumors and provide evidence suggesting that targeted inhibition of ER-α signaling may be useful for the prevention of BRCA1-mutated breast cancer.

KeywordBrca1 Cancer Prevention Estrogen Fulvestrant
DOI10.7150/ijbs.28142
URLView the original
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics
WOS SubjectBiochemistry & Molecular Biology ; Biology
WOS IDWOS:000447937900016
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Cited Times [WOS]:1   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Co-First AuthorBaek H.J.
Corresponding AuthorKim S.S.
Affiliation1.Gachon University
2.National Cancer Center, Gyeonggi
3.Universidade de Macau
Recommended Citation
GB/T 7714
Baek H.J.,Kim S.E.,Choi E.K.,et al. Inhibition of Estrogen Signaling Reduces the Incidence of BRCA1-associated Mammary Tumor Formation[J]. International journal of biological sciences,2018,14(12):1755-1768.
APA Baek H.J..,Kim S.E..,Choi E.K..,Kim J.K..,Shin D.H..,...&Kim S.S..(2018).Inhibition of Estrogen Signaling Reduces the Incidence of BRCA1-associated Mammary Tumor Formation.International journal of biological sciences,14(12),1755-1768.
MLA Baek H.J.,et al."Inhibition of Estrogen Signaling Reduces the Incidence of BRCA1-associated Mammary Tumor Formation".International journal of biological sciences 14.12(2018):1755-1768.
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