FGFR2 AND RUNX2 PROMOTE BREAST CANCER PROGRESSION IN HUMAN BREAST CANCER MODELS

RODRÍGUEZ, MARÍA SOL; GIULIANELLI, SEBASTIÁN; GUILLARDOY, TOMÁS; LAMB, CAROLINE A.; LUTHY, ISABEL; LANARI, CLAUDIA; PÉREZ PIÑERO, CECILIA

Congreso; Sociedad Argentina de Investigación Clínica; 2021

We have previously shown that FGF2 increases the proliferationof breast cancer cells activating FGFR2 and ligand-independenthormone receptor signaling. FGF/FGFR alterations are frequentin breast cancer patients, and for this reason, FGFR inhibitors arebeing evaluated to overcome endocrine resistance. In addition, apositive loop between FGF2 and RUNX2 has been shown in bonetissue. Thus, our aim was to evaluate the interplay between FGFR2and RUNX2 in luminal human breast cancer models in responseto endocrine or FGFR-targeted therapies. We stably transfectedMCF7 and T47D cells with a constitutively active FGFR2 (R2CA),a RUNX2 expression plasmid, or an empty vector (Control). R2CAand RUNX2 cells grow in vivo without hormone supply. R2CA cellsshow phosphorylated estrogen (ER) and progesterone receptors(PR) and higher RUNX2 levels as compared with control cells.RUNX2 cells express lower levels of estrogen receptor (ER) andhigher levels of FGFR2 as compared with control cells. Both, R2CAand RUNX2 tumors give rise to lung metastasis, absent in controlmice. The antiestrogen Fulvestrant (p