RUNX2 REGULATES THE HORMONE REQUIREMENT AND THE MESTASTATIC POTENCIAL OF T47D BREAST CANCER CELLS IN VIVO.

LANARI C; RODRIGUEZ, M.S; PÉREZ CECILIA

Ciudad de Buenos Aires

Congreso; Reunión Conjunta de Sociedades de BioCiencias; 2017

Sociedad Argentina de Investigación Clínica

We have previously shown that FGF2 increases the proliferation of MCF-7 and T47D breast cancer cells activating FGFR2, progesterone and estrogen receptors alpha (PR and ERα respectively). It has been reported that FGF2 increases RUNX2 expression in bone cells and few reports suggest that this might also occur in breast cancer cells. Since high RUNX2 levels were detected in murine mammary carcinomas which acquired a hormone independent phenotype, we are currently exploring the role of the FGF2-FGFR-RUNX2 axis in breast cancer progression.The aim of this study was to evaluate if RUNX2 overexpression was able to bypass the hormone requirement of non metastatic T47D breast cancer xenografts which express ERα and PR. We stably transfected T47D cells with an expression plasmid carrying RUNX2 (RUNX2 cells) or with the empty vector (control cells). RUNX2 cells showed an increase in FGFR2 and FGF2 expression, supporting the hypothesis that FGF2 increases RUNX2, and RUNX2, in turn increases FGF2 expression, maintaining a positive loop. Both cell types were s.c. inoculated with Geltrex into the flank of NSG mice in the presence or absence of 17-β-Estradiol (E2 pellets; 0.5 mg). In untreated mice, only RUNX2 cells proved to be tumorigenic, although tumors remained with small sizes during the experiment. In E2-treated mice, RUNX2 xenografts grew faster and with a more aggressive phenotype as compared with control tumors (p