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Elevated GCN5 expression confers tamoxifen resistance by upregulating AIB1 expression in ER-positive breast cancer

Authors
 Ji Hoon Oh  ;  Ji-Yeon Lee  ;  Kwang H Kim  ;  Clara Yuri Kim  ;  Da Som Jeong  ;  Yejin Cho  ;  Ki Taek Nam  ;  Myoung Hee Kim 
Citation
 CANCER LETTERS, Vol.495 : 145-155, 2020-12 
Journal Title
 CANCER LETTERS 
ISSN
 0304-3835 
Issue Date
2020-12
Keywords
Histone acetyltransferase ; KAT2A ; NCOA3 ; p21 ; p53
Abstract
Approximately 70% of breast cancers are estrogen receptor (ER)-positive and treated with endocrine therapy. A commonly used treatment agent, tamoxifen, shows high efficacy for improving prognosis. However, approximately one-third of patients treated with tamoxifen develop resistance to this drug. Here, we investigated the function of general control non-derepressible 5 (GCN5) and its downstream effectors in tamoxifen-resistant (TamR) breast cancer. TamR-MCF7 breast cancer cells maintained high GCN5 levels due to its attenuated proteasomal degradation. GCN5 overexpression upregulated amplified in breast cancer 1 (AIB1) expression, resulting in decreased p53 stability and tamoxifen resistance. Conversely, the sensitivity of GCN5-AIB1-overexpressing MCF7 cells to tamoxifen was restored by forced p53 expression. An in vivo study demonstrated a positive correlation between GCN5 and AIB1 and their contribution to tamoxifen resistance. We concluded that GCN5 promotes AIB1 expression and tamoxifen resistance in breast cancer by reducing p53 levels, suggesting the utility of GCN5 and its downstream effectors as therapeutic targets to either prevent or overcome tamoxifen resistance in breast cancer.
Full Text
https://www.sciencedirect.com/science/article/pii/S0304383520304894
DOI
10.1016/j.canlet.2020.09.017
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kim, Myoung Hee(김명희) ORCID logo https://orcid.org/0000-0001-5652-1452
Kim, Clara Yuri(김유리)
Nam, Ki Taek(남기택)
Oh, Ji Hoon(오지훈) ORCID logo https://orcid.org/0000-0001-6619-5515
Lee, Ji Yeon(이지연) ORCID logo https://orcid.org/0000-0002-0670-3095
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/180651
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