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

RODRIGUEZ, MARIA SOL; GIULIANELLI, SEBASTIÁN; GUILLARDOY, TOMAS; LAMB, CAROLINE; LUTHY, ISABEL; LANARI, CLAUDIA; PEREZ PIÑERO, CECILIA

Mar del Plata

Congreso; Reunion Conjunta SAIC SAI AAFE NANOMED.ar; 2021

We have previously shown that FGF2 increases the proliferation of breast cancer cellsactivating FGFR2 and ligand-independent hormone receptor signaling. FGF/FGFRalterations are frequent in breast cancer patients, and for this reason, FGFR inhibitorsare being evaluated to overcome endocrine resistance. In addition, a positive loopbetween FGF2 and RUNX2 has been shown in bone tissue. Thus, our aim was toevaluate the interplay between FGFR2 and RUNX2 in luminal human breast cancermodels in response to endocrine or FGFR-targeted therapies. We stably transfectedMCF7 and T47D cells with a constitutively active FGFR2 (R2CA), a RUNX2expression plasmid, or an empty vector (Control). R2CA and RUNX2 cells grow invivo without hormone supply. R2CA cells show phosphorylated estrogen (ER) andprogesterone receptors (PR) and higher RUNX2 levels as compared with control cells.RUNX2 cells express lower levels of estrogen receptor (ER) and higher levels ofFGFR2 as compared with control cells. Both, R2CA and RUNX2 tumors give rise tolung metastasis, absent in control mice. The antiestrogen Fulvestrant (p