ID4 ACTS AS A TUMOR SUPPRESSOR IN ER+ BREAST TUMORS

DANIELA L. NASIF; SERGIO LAURITO; URRUTIA, GUILLERMO; BRANHAM, MARÍA TERESITA; CAMPOY,EMANUEL; ROQUÉ MORENO, MARÍA

Mar del Plata, Buenos Aires

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC; 2016

SAIC

Inhibitor of differentiation proteins 1, 2, 3 and 4 (ID1?4), are dominant negative regulators of the basic helix-loop helix (bHLH) family of transcription factors. In human tumors, an increased expression of ID proteins has been associated with reversion to an embryonic-like state, loss of differentiation, high rates of proliferation, migration and neo-angiogenesis. In breast cancer there are controversial findings regarding the role of ID4 during tumorigenesis. For instance, ID4 silencing by promoter hypermethylation is a frequent event in ER+ (estrogen receptor) breast tumors and is associated with an increased risk of lymph node metastasis. However, in ER- breast tumors ID4 increased expression has been associated with the ability of cancer cells to exhibit anchorage-independent growth. Our group has previously shown that ID4 promoter?s unmethylation is associated with the aggressive Triple Negative Breast cancer subtype. It seems then, that ID4 has a dual role in breast cancer. Here, we hypothesize that ID4 acts as a tumor suppressor in ER+ breast tumors. To test our hypothesis we performed data mining analyses from the TCGA database and cell culture experiments. In silico analyses, in a cohort of 872 invasive ductal breast carcinomas, reveal that ID4 is downregulated in ER+ breast tumors (p