Differential expression of FGFR-1 and -2 in hormone responsive and resistant murine mammary carcinomas.

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

Washington

Congreso; AACR Annual 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. The aim of this study is to investigate the expression of FGF2, FGFR1, FGFR2 in C4-HI, C4-HIR and C4-2-HI tumor variants. By immunohistochemistry and western blot we observed a decrease in FGFR2 expression for C4-2-HI (p