INVESTIGADORES
SAHORES Ana
congresos y reuniones científicas
Título:
Differential expression of FGFR-1 and -2 in hormone responsive and resistant murine mammary carcinomas
Autor/es:
ANA SAHORES, M.S.; TOMÁS GUILLARDOY; VICTORIA WARGON; CLAUDIA LANARI; CAROLINE LAMB
Lugar:
Washington DC
Reunión:
Congreso; AACR; 2013
Institución organizadora:
AACR
Resumen:
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<0.001) and C4-HIR (p<0.01) as compared to
C4-HI. Moreover, we found an increased expression of FGF2 and FGFR1 by western
blot (p<0.05) and immunohistochemistry in the epithelium of the resistant
tumor variants. Similar results were obtained with another family of
antiprogestin responsive and unresponsive tumors (59-HI and 59-2-HI). These data suggest
that in this mammary tumor model hormone resistance may be characterized by a switch
from paracrine to autocrine FGF2 signaling together with a decrease in FGFR2 and an
increase in FGFR1. These results contribute to understand the role of the FGFR
pathway in hormone resistance and support the use of FGFR inhibitors combined
with hormonal therapy to delay the onset of hormone resistance.