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- W2069895246 abstract "Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DCFibroblast 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.Citation Format: Ana Sahores, Tomas Guillardoy, Victoria Wargon, Claudia Lanari, Caroline Lamb. Differential expression of FGFR-1 and -2 in hormone responsive and resistant murine mammary carcinomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 532. doi:10.1158/1538-7445.AM2013-532" @default.
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- W2069895246 date "2013-04-15" @default.
- W2069895246 modified "2023-09-26" @default.
- W2069895246 title "Abstract 532: Differential expression of FGFR-1 and -2 in hormone responsive and resistant murine mammary carcinomas." @default.
- W2069895246 doi "https://doi.org/10.1158/1538-7445.am2013-532" @default.
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