Interplay between Epigenetics, Expression of Estrogen Receptor- α, HER2/ERBB2 and Sensitivity of Triple Negative Breast Cancer Cells to Hormonal Therapy

• Main Authors: Wafaa S Ramadan, Cijo George Vazhappilly, Ekram M Saleh, Varsha Menon, Aya M AlAzawi, Ahmed T El-Serafi, Wael Mansour, Raafat El-Awady
• Format: Article
• Language: English
• Published: MDPI AG 2018-12-01
• Series: Cancers
• Subjects: triple negative breast cancer; estrogen receptor alpha; human epidermal growth factor receptor-2; epigenetics; suberoylanilide hydroxamic acid; 2′-deoxy-5-azacytidine; tamoxifen
• Online Access: http://www.mdpi.com/2072-6694/11/1/13
• ISSN: 2072-6694

Triple negative breast cancer (TNBC) cells are resistant to hormonal/targeted therapies. This study aims to investigate epigenetic differences between TNBC and other types of breast cancer and the effect of epigenetic modulation on the response of TNBC cells to hormonal therapy. Thus, we investigated (i) the expression of different epigenetic markers, (ii) the effect of epigenetic modifying agents on the expression of ERα and HER2/ERBB2 and (iii) the effect on the response to tamoxifen in four breast cancer cell lines with different hormonal receptor status. Our results revealed a differential expression patterns of epigenetic markers in the four breast cancer cells. In TNBC cells, histone deacetylases (HDAC) 1 and 2 were less expressed, whereas HDACs 4 and 6 were overexpressed. Interestingly, treatment with epigenetic modifiers resulted in (i) a pronounced increase in the expression of ERα and HER2/ERBB2 along with (ii) an increase in the sensitivity of TNBC cells to tamoxifen. Collectively, this study indicates a different epigenetic background for TNBC cells, which represses the expression of ERα and HER2/ERBB2. Furthermore, we provide here the rationale for the use of epigenetic modifiers to enhance the response of TNBC to hormonal therapy through upregulation of ERα.