Eviction of NErbB-2 in the presence of activated androgen receptor (AR) defines a gene signature associated with favorable outcome in TNBC

ROLDAN DE-AMICIS, A; OACKLEY R; ANDONEGUI HELGUERA S; LENZE M; MADERA S; CORDO RUSSO R; CHERVO MARÍA F; SCHILLACI R; FRESNO C; CIDLOWSKI JA; ELIZALDE P V; PROIETTI CJ

Simposio; Cancer Cell Symposium: Overcaming Therapy Resistance in Cancer; 2021

We propose there is an interaction between AR and ErbB-2 which is involved in NErbB-2+/AR+ BC growth. We found that dihydrotestosterone (DHT) treatment increased Tyr877-ErbB-2 and induced ErbB-2 nuclear migration. By chIP we found that DHT induced ErbB-2 recruitment to a HAS site in FKBP5, an AR responsive gene. By microarray we identified 315 differentially expressed genes in the presence of DHT and NErbB-2 eviction by transfection with an ErbB-2 mutant which is unable to translocate to the nucleus and functions as a dominant-negative inhibitor of ErbB-2 nuclear migration. Multivariate Cox regression analysis identified the combined expression of CXCL10, TAP1, STAT1, NMI, and HLA-A as an independentpredictor of better clinical outcome in TNBC. In conclusion, our findings evidenced that activated AR induces ErbB-2 activation and migration to the nucleus where it binds to HAS sites in DNA. Moreover, we identified a gene signature associated with favorable outcome in TNBC.