HDAC5 Inhibitors as a Potential Treatment in Breast Cancer Affecting Very Young Women

被引:14
|
作者
Oltra, Sara S. [1 ]
Miguel Cejalvo, Juan [1 ]
Tormo, Eduardo [1 ,2 ]
Albanell, Marta [1 ]
Ferrer, Ana [1 ]
Nacher, Marta [1 ]
Bermejo, Begona [1 ]
Hernando, Cristina [1 ]
Chirivella, Isabel [1 ]
Alonso, Elisa [2 ,3 ]
Burgues, Octavio [2 ,3 ]
Pena-Chilet, Maria [1 ]
Eroles, Pilar [1 ,2 ]
Lluch, Ana [1 ,2 ]
Ribas, Gloria [1 ,2 ]
Teresa Martinez, Maria [1 ]
机构
[1] Univ Valencia, Hosp Clin Univ Valencia, INCLIVA Biomed Res Inst, Valencia 46010, Spain
[2] Biomed Res Ctr Network Canc CIBERONC, Valencia 46010, Spain
[3] Univ Valencia, Hosp Clin Univ Valencia, Pathol Dept, Valencia 46010, Spain
关键词
breast cancer; young women; histone deacetylase; HDAC5; inhibitors; LMK-235; HISTONE DEACETYLASES; ESTROGEN-RECEPTOR; EXPRESSION; PREDICTOR; PROFILE; DISEASE;
D O I
10.3390/cancers12020412
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Breast cancer in very young women (BCVY) defined as <35 years old, presents with different molecular biology than in older patients. High HDAC5 expression has been associated with poor prognosis in breast cancer (BC) tissue. We aimed to analyze HDAC5 expression in BCVY and older patients and their correlation with clinical features, also studying the potential of HDAC5 inhibition in BC cell lines. Methods: HDAC5 expression in 60 BCVY and 47 older cases were analyzed by qRT-PCR and correlated with clinical data. The effect of the HDAC5 inhibitor, LMK-235, was analyzed in BC cell lines from older and young patients. We performed time and dose dependence viability, migration, proliferation, and apoptosis assays. Results: Our results correlate higher HDAC5 expression with worse prognosis in BCVY. However, we observed no differences between HDAC5 expression and pathological features. Our results showed greatly reduced progression in BCVY cell lines and also in all triple negative subtypes when cell lines were treated with LMK-235. Conclusions: In BCVY, we found higher expression of HDAC5. Overexpression of HDAC5 in BCVY correlates with lower survival rates. LMK-235 could be a potential treatment in BCVY.
引用
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页数:14
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