ID4 ACTS AS A TUMOR SUPPRESSOR IN ER+ BREAST TUMORS

NASIF DANIELA; CAMPOY, EMANUEL; URRUTIA GUILLERMO; LAURITO SERGIO; ROQUÉ MARIA; BRANHAM MARIA T

Mar del Plata

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

Inhibitor of differentiation proteins1, 2, 3 and 4 (ID1?4), aredominant negative regulators of the basic helix-loop helix (bHLH)  family  of transcription factors.  In  human  tumors, an increased expressionof ID proteins has been associatedwith reversion to an embryonic-like state, loss of differentiation, high rates ofproliferation, migration and neo-angiogenesis.  In breast cancer thereare controversial findingsregarding the role of +& during tumorigenesis. For instance, ID4 silencingby promoter hypermethylation is  a frequent  event  in ER+  (estrogen  receptor) breast  tumors and is associated withan increased risk of lymph node  metastasis.   However,  in  ER-  breast tumors  ID4  increasedexpression has been associated with the ability of cancer cells to exhibitanchorage-independent growth. Our  group has  previously  shown that  ID4  promoter?s unmethylation  is associated  with  the aggressive  Triple  NegativeBreast cancer subtype. It seems then, that ID4 has a dual role in breastcancer.  Here, we hypothesize that ID4 acts as a tumor suppressorin ER+ breast tumors. To testour hypothesis we performed data mining analyses from the TCGA database andcell culture experiments. In silicoanalyses, in a cohort of 872 invasive ductal breast carcinomas,  reveal that  ID4  is downregulated  in  ER+  breast tumors (p<0,001) dueto promoter methylation. To testthe effect of ectopic ID4 expression, we performed ID4 transient transfection onMCF-7 and T47D breast cancer celllines. Both are ER+, present ID4 promoter methylation and do not express ID4.  Ectopic ID4 expression on MCF-7 and  T47D  cells  lead to decreased  proliferation  and  increased apoptosis.  Cell  cycle analysis  indicated  thatID4 transfected cells accumulated in G1 phase. ID4 overexpression  also  reduced migration  rate respect  to  cells treated with an empty vector. Theresults presented suggestthat ID4 acts as a tumor suppressor in ER+ tumors by leading to reduced proliferationand migration in breast cancer cell lines.