CDC42 REVERTS AGGRESSIVENESS OF A TRIPLE NEGATIVE BREAST CANCER CELL LINE TROUGH METHYLATION OF ID4 PROMOTER

NASIF, DANIELA; LAURITO, SERGIO; CAMPOY, EMANUEL MARTIN; ROQUÉ, MARÍA; BRANHAM, MARIA TERESITA

Mar del Plata

Congreso; LXII Reunión Científica Anual de la SAIC; 2017

Sociedad Argentina de Investigación Clínica

Breast cancer (BC) is one of the most prevalent tumors and a leading cause of death in women worldwide. There are several clinical types of BC, defined by amplification of specific markers. Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by the absence of ER, PgR and HER2. Accelerated growth, high recurrence rates, and frequent metastasis characterize the aggressiveness of TNBC and result in poor long-term patient survival. ID4 (Inhibitor of DNA binding 4) is a member of the ID family and several evidence suggest that it plays an important role during tumorigenesis. Specifically in breast cancer, there are controversial findings given that both, a tumor suppressor and an oncogenic function have been attributed to this protein. Particularly in TNBC it has been shown by us and other groups, that ID4 is overexpressed due to promoter unmethylation and that ID4 downregulates BRCA1 expression in these tumors. Our group has also demonstrated that ID4?s unmethylated status is associated with BRCA-ness phenotype in TNB tumors. Since our hypothesis is that ID4 has an oncogenic function in TNBC, we attempted to silence ID4 expression trough the methylation of its promoter. The small GTPase Cdc42 has been described as an effector of ID4 methylation. Here we show that the overexpression of Cdc42 reduced TNBC aggressive phenotype through the methylation of ID4 promoter and upregulation of BRCA1.