"Role of FGF2 pathway in murine hormone resistant mammary carcinomas"

SAHORES, ANA; WARGON, VICTORIA; LANARI, CLAUDIA; LAMB, CAROLINE A.

Congreso; AACR Breast Cancer Meeting; 2013

Fibroblast growth factor (FGF) receptors (FGFRs) are dysregulated in a number of developmental and neoplastic conditions. In human breast cancer samples we have previously demonstrated a significant association between FGFR2 expression and estrogen receptors as well as a positive correlation of FGFR1 and high histological grade. Most breast carcinomas that express hormone receptors respond initially to an endocrine therapy, but over time, they develop resistance (acquired hormone resistance). Others fail to respond from the beginning (constitutive resistance). Using a breast cancer mouse model, we have previously demonstrated that antiprogestin-responsive tumors (C4-HI) show a higher expression level of progesterone receptor isoform A than PR isoform B (PRB), while tumors with constitutive (C4-2-HI) or acquired resistance (C4-HIR) to antiprogestins, display a higher expression level of PRB. Moreover, we have demonstrated, in an antiprogestin-responsive tumor that FGFR2 activated by FGF2 released by the stromal compartment participate in tumor growth activating PR. In recent experiments, we observed a decreased expression of FGFR2 in hormone resistant compared to hormone responsive variants. Conversely, we found an increased expression of FGF2 and FGFR1 in hormone resistant variants. The aim of this study is to evaluate the role of the FGF2-pathway in hormone resistant tumor variants. In primary cultures from hormone resistant C4-2-HI epithelial cells, we found that FGF2 (100 ng/ml) significantly increased cell proliferation (p