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Cyclin B1 stability is increased by interaction with BRCA1, and its overexpression suppresses the progression of BRCA1-associated mammary tumors
Choi, Eun Kyung1; Lim, Jeong-A1; Kim, Jong Kwang1; Jang, Moon Sun1; Kim, Sun Eui1; Baek, Hye Jung1; Park, Eun Jung1; Kim, Tae Hyun1; Deng, Chu-Xia2; Wang, Rui-Hong2; Kim, Sang Soo1
2018-10-16
Source PublicationExperimental and Molecular Medicine
ISSN1226-3613
Volume50Pages:136
Abstract

Germline BRCA1 mutations predispose women to breast and ovarian cancer. BRCA1, a large protein with multiple functional domains, interacts with numerous proteins involved in many important biological processes and pathways. However, to date, the role of BRCA1 interactions at specific stages in the progression of mammary tumors, particularly in relation to cell cycle regulation, remains elusive. Here, we demonstrate that BRCA1 interacts with cyclin B1, a crucial cell cycle regulator, and that their interaction is modulated by DNA damage and cell cycle phase. In DNA-damaged mitotic cells, BRCA1 inhibits cytoplasmic transportation of cyclin B1, which prevents cyclin B1 degradation. Moreover, restoration of cyclin B1 in BRCA1-deficient cells reduced cell survival in association with induction of apoptosis. We further demonstrate that treatment of Brca1-mutant mammary tumors with vinblastine, which induces cyclin B1, significantly reduced tumor progression. In addition, a correlation analysis of vinblastine responses and gene expression profiles in tumors at baseline revealed 113 genes that were differentially expressed between tumors that did and did not respond to vinblastine treatment. Further analyses of protein-protein interaction networks revealed gene clusters related to vinblastine resistance, including nucleotide excision repair, epigenetic regulation, and the messenger RNA surveillance pathway. These findings enhance our understanding of how loss of BRCA1 disrupts mitosis regulation through dysregulation of cyclin B1 and provide evidence suggesting that targeting cyclin B1 may be useful in BRCA1-associated breast cancer therapy.

DOIhttp://doi.org/10.1038/s12276-018-0169-z
URLView the original
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Research & Experimental Medicine
WOS SubjectBiochemistry & Molecular Biology ; Medicine, Research & Experimental
WOS IDWOS:000447546200001
PublisherNATURE PUBLISHING GROUP
The Source to ArticleWOS
Fulltext Access
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Cited Times [WOS]:1   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorWang, Rui-Hong; Kim, Sang Soo
Affiliation1.Research Institute, National Cancer Center, Goyang 10408, Korea
2.Cancer Centre, Faculty of Health Sciences, University of Macau, Macau 999078, China
Corresponding Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Choi, Eun Kyung,Lim, Jeong-A,Kim, Jong Kwang,et al. Cyclin B1 stability is increased by interaction with BRCA1, and its overexpression suppresses the progression of BRCA1-associated mammary tumors[J]. Experimental and Molecular Medicine,2018,50:136.
APA Choi, Eun Kyung.,Lim, Jeong-A.,Kim, Jong Kwang.,Jang, Moon Sun.,Kim, Sun Eui.,...&Kim, Sang Soo.(2018).Cyclin B1 stability is increased by interaction with BRCA1, and its overexpression suppresses the progression of BRCA1-associated mammary tumors.Experimental and Molecular Medicine,50,136.
MLA Choi, Eun Kyung,et al."Cyclin B1 stability is increased by interaction with BRCA1, and its overexpression suppresses the progression of BRCA1-associated mammary tumors".Experimental and Molecular Medicine 50(2018):136.
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