NErbB-2 and Androgen Receptor Regulate a Gene Signature Involved in Immune Response and Favorable Outcome in TNBC

CECILIA PROIETTI, AGUSTINA ROLDAN DEAMICIS, ROBERT OAKLEY, SANTIAGO MADERA, ROSALÍA CORDO RUSSO, ROXANA SCHILLACI, CRISTÓBAL FRESNO, JOHN CIDLOWSKI, PATRICIA V ELIZALDE.

Atlanta

Congreso; 104th Annual Meeting of the Endocrine Society.; 2022

Triple negative breast cancer (TNBC) has poor prognosis and neither established biomarkers nor therapeutic targets. On the one hand the androgen receptor (AR), a steroid hormone receptor (SR) which is expressed in 10-53% of TNBC and proved to be critical for BC proliferation, has been proposed as a new target in TNBC. On the other hand, we and others have shown that membrane ErbB-2 migrates to the nucleus (nuclear ErbB-2, NErbB-2) where it binds DNA at HER-2 associated sequences (HAS) to regulate BC proliferation and migration. Since we have previously shown a functional interplay between growth factors and SR signaling pathways in BC, we propose the existence of an interaction between AR and ErbB-2 which is involved in NErbB-2+/AR+ BC growth and which ultimately takes place at the chromatin level. Moreover, based on the DEGs of NErbB-2 eviction in presence of DHT, we identified a gene signature associated with favorable outcome which is composed of genes involved in the immune response in TNBC.