WNT PATHWAY DYSREGULATION AND ITS RELEVANCE IN ENDOCRINE RESISTANT BREAST CANCER MODELS Marcela Coianis1, VirginiaFigueroa1, Gabriela Pataccini1, Silvia Vanzulli2, Claudia Lanari1, Caroline A. Lamb1. 1: Instituto de Biología y Medicina Experimental (IBYM

MARCELA COIANIS; VIRGINIAFIGUEROA; GABRIELA PATACCINI; SILVIA VANZULLI; CLAUDIA LANARI; CAROLINE A. LAMB

Mar del Plata

Congreso; Sociedad argentina de investigación clínica; 2022

Endocrine therapy is the standard treatment for patients with luminal breast cancer. However, after treatment most patients develop hormone resistance, by mechanisms that may include dysregulation of growth factor signaling pathways. Fibroblast growth factor 2 (FGF2) consists of a secreted low molecular weight form and several nuclear high molecular weight forms (HMW-FGF2). We previously demonstrated that HMW-FGF2-overexpression in endocrine responsive T47D cell lines, induced hormone resistance, dysregulation of the WNT signaling pathway and an increase in androgen receptor (AR) expression. We hypothesize that FGF2 induces WNT pathway activation which, in turn, induces AR expression. The aim of this study was to evaluate the expression of downstream effectors of the WNT/β-catenin pathway in endocrine resistant breast cancer models to assess if targeting this pathway may be an effective treatment for these tumors. We used the endocrine resistant T47D-HMW-FGF2 and T47D-YB cell lines, the latter naturally expressing higher levels of HMW-FGF2 than the responsive T47D cells, to determine the expression of different WNT/β-catenin effectors compared with the parental cell lines growing in vitro and/or in vivo. T47D-HMW-FGF2 tumors expressed significantly higher levels of WNT4, DVL3 and AXIN1 while T47D-YB cells expressed higher DVL2 levels compared to control cells (p