WNT PATHWAY DYSREGULATION AND ITS RELEVANCE IN ENDOCRINE RESISTANT BREAST CANCER MODELS

COIANIS, MARCELA; FIGUEROA, VIRGINIA; PATACCINI, GABRIELA; VANZULLI, SILVIA I.; LANARI, CLAUDIA; LAMB, CAROLINE A.

Mar del Plata

Congreso; Sociedad Argentina de Investigación Clínica; 2022

Endocrine therapy is the standard treatment for patients with luminalbreast cancer. However, after treatment most patients develophormone resistance, by mechanisms that may include dysregulationof growth factor signaling pathways. Fibroblast growth factor 2(FGF2) consists of a secreted low molecular weight form and severalnuclear high molecular weight forms (HMW-FGF2). We previouslydemonstrated that HMW-FGF2-overexpression in endocrineresponsive T47D cell lines, induced hormone resistance, dysregulationof the WNT signaling pathway and an increase in androgenreceptor (AR) expression. We hypothesize that FGF2 induces WNTpathway activation which, in turn, induces AR expression. The aimof this study was to evaluate the expression of downstream effectorsof the WNT/β-catenin pathway in endocrine resistant breastcancer models to assess if targeting this pathway may be an effectivetreatment for these tumors. We used the endocrine resistantT47D-HMW-FGF2 and T47D-YB cell lines, the latter naturallyexpressing higher levels of HMW-FGF2 than the responsive T47Dcells, to determine the expression of different WNT/β-catenin effectorscompared with the parental cell lines growing in vitro and/or invivo. T47D-HMW-FGF2 tumors expressed significantly higher levelsof WNT4, DVL3 and AXIN1 while T47D-YB cells expressed higherDVL2 levels compared to control cells (p