UM  > 健康科學學院
Inhibition of AKT suppresses the initiation and progression of BRCA1-associated mammary tumors
Baek H.J.2; Kim S.E.2; Kim J.K.2; Shin D.H.2; Kim T.H.2; Kim K.G.1; Deng C.-X.3; Kim S.S.2
2018
Source PublicationInternational journal of biological sciences
ISSN14492288
Volume14Issue:13Pages:1769-1781
Abstract

Despite the high incidence of BRCA1-mutant breast cancer, few substantial improvements in preventing or treating such cancers have been made. Using a Brca1-mutant mouse model, we examined the contribution of AKT to the incidence and growth of Brca1-mutated mammary tumors. A haploinsufficiency of Akt1 in Brca1-mutant mouse model significantly decreased mammary tumor formation from 54% in Brca1co/coMMTV-Cre mice to 22% in Brca1 co/coMMTV-Cre Akt1+/- mice. Notably, treatment of tumor-bearing Brca1-mutant mice with the AKT-inhibitor, MK-2206, yielded partial response or stable disease up to 91% of mice in maximum response. MK-2206 treatment also significantly reduced tumor volume and delayed recurrence in allograft and adjuvant studies, respectively. A correlation analysis of MK-2206 responses with gene expression profiles of tumors at baseline identified seven genes that were differentially expressed between tumors that did and did not respond to MK-2206 treatment. Our findings enhance our understanding of the involvement of AKT signaling in BRCA1-deficient mammary tumors and provide preclinical evidence that targeted AKT inhibition is a potential strategy for the prevention and therapeutic management of BRCA1-associated breast cancer.

KeywordAkt Brca1 Mk-2206 Precision Medicine
DOI10.7150/ijbs.29242
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:000452059900001
Fulltext Access
Citation statistics
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.,Kim J.K.,et al. Inhibition of AKT suppresses the initiation and progression of BRCA1-associated mammary tumors[J]. International journal of biological sciences,2018,14(13):1769-1781.
APA Baek H.J..,Kim S.E..,Kim J.K..,Shin D.H..,Kim T.H..,...&Kim S.S..(2018).Inhibition of AKT suppresses the initiation and progression of BRCA1-associated mammary tumors.International journal of biological sciences,14(13),1769-1781.
MLA Baek H.J.,et al."Inhibition of AKT suppresses the initiation and progression of BRCA1-associated mammary tumors".International journal of biological sciences 14.13(2018):1769-1781.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Baek H.J.]'s Articles
[Kim S.E.]'s Articles
[Kim J.K.]'s Articles
Baidu academic
Similar articles in Baidu academic
[Baek H.J.]'s Articles
[Kim S.E.]'s Articles
[Kim J.K.]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Baek H.J.]'s Articles
[Kim S.E.]'s Articles
[Kim J.K.]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.