ESTROGEN RECEPTOR-ID4 CROSS TALK IN BREAST CANCER

ROQUÉ MORENO, MARÍA; DANIELA L. NASIF; BRANHAM, MARÍA TERESITA

Buenos Aires

Congreso; Reunion anual de sociedades de biociencia SAIC-SAI-SAFE-2020; 2020

Sociedad Argentina de Investigación Clínica

Inhibitor of differentiation (ID) 4, a member of the ID family, has been shown to act as a tumorsuppressor and as an oncogene in breast cancer. Our group has investigated this apparentdiscordant information and have found evidence that ID4 acts as a tumor suppressor only inestrogen receptor (ER)+ tumors and as an oncogene only in ER- tumors. Here we focus on ID4?stumor suppressor role and further investigate why ID4 is aberrantly methylated exclusively inER+ tumors. EZH2 is a histone methyl transferase involved in the tri-methylation of lysine 27on histone 3 (H3K27me3) and also promotes DNA methylation via DNMT recruitment. Inbreast cancer EZH2 is overexpressed and downregulates the expression of tumor suppressorgenes via increased promoter H3K27me3. Since ID4 is hyper-methylated in ER+ tumors andsince EZH2 expression is induced by estradiol we hypothesize that estradiol induces ID4methylation through EZH2. We performed siRNA (EZH2), immunofluorescence and chromatinimmunoprecipitation (CHIP) experiments in MCF7 breast cancer cell lines. Our results showthat EZH2 regulates ID4 expression as confirmed by siRNA experiments, that estrogentreatment increases EZH2 expression and ID4 methylation and CHIP experiments reveal thatestrogen administration increases EZH2 and H3K27me3 marks on ID4 promoter. Takentogether our results show for the first time that estradiol induces ID4 methylation trough EZH2in breast cancer cell lines.