CDC42 as an epigenetic regulator of ID4 in breast cancer

NASIF DANIELA; LAURITO SERGIO; ROQUÉ MARIA; BRANHAM MARIA T

Aguas de Lindoia

Congreso; 48th Annual Meeting of the Brazilian Society of Biochemistry and Molecular Biology (SBBq); 2019

Breast cancer can be classified as luminal A, luminal B, human epidermal growth factor receptor 2 and triple-negative (TN). Clinically, TN subtype has an aggressive nature, higher rates of relapse and shorter overall survival. Inhibitor of differentiation proteins 1, 2, 3 and 4 (ID1?4), are dominant negative regulators of the basic helix-loop helix family of transcription factors. In TN tumors, increased expression of ID4 proteins has been associated with reversion to an embryonic-like state, high rates of proliferation and migration. We have shown that ID4 promoter hypomethylation is associated with TN subtype. Also, that ID4 hypomethylation is associated with BRCAness phenotype and BRCA1 downregulation. Cdc42 is a plasma membrane-associated small GTPase, whose expression is dysregulated in several tumor types. Here we show that the overexpression of CDC42 reduced the aggressive phenotype of the MDA-MB-231 cells through the methylation of ID4 promoter and upregulation of BRCA1. Methods and Results: MDA-MB321 cell lines were transfected with a CDC42-GFP vector. ID4 methylation was measured by droplet digital, MS PCR and MS-MLPA assay. ID4 methylation increased after CDC42 transfection (p