Associated expressions of FGFR-2 and FGFR-3: from mouse mammary gland physiology to human breast cancer.

CERLIANI JUAN PABLO; VANZULLI SILVIA I.; PEREZ PIÑERO CECILIA; BOTTINO MARÍA C; SAHORES ANA; NUÑEZ MYRIAM; VARCHETTA ROMINA ; MARTINS RUBÉN; ZEITLIN EDUARDO; HEWITT STEPHEN M.; MOLINOLO ALFEDRO A. ; LANARI CLAUDIA; LAMB CAROLINE

BREAST CANCER RESEARCH AND TREATMENT

SPRINGER

Año: 2012 vol. 133 p. 997 - 1008

0167-6806

Fibroblast growth factor receptors (FGFRs) are tyrosine kinase receptors which have been implicated in breast cancer. The aim of this study was to evaluate FGFR-1, -2, -3, and -4 protein expressions in normal murine mammary gland development, and in murine and human breast carcinomas. Using immunohistochemistry and Western blot, we report a hormonal regulation of FGFR during postnatal mammary gland development. Progestin treatment of adult virgin mammary glands resulted in changes in localization of FGFR-3 from the cytoplasm to the nucleus, while treatment with 17-β-estradiol induced changes in the expressions and/or localizations of FGFR-2 and -3. In murine mammary carcinomas showing different degrees of hormone dependence, we found progestin-induced increased expressions, mainly of FGFR-2 and -3. These receptors were constitutively activated in hormone-independent variants. We studied three luminal human breast cancer cell lines growing as xenografts, which particularly expressed FGFR-2 and -3, suggesting a correlation between hormonal status and FGFR expression. Most importantly, in breast cancer samples from 58 patients, we found a strong association (P < 0.01; Spearman correlation) between FGFR-2 and -3 expressions and a weaker correlation of each receptor with estrogen receptor expression. FGFR-4 correlated with c-erbB2 over expression. We conclude that FGFR-2 and -3 may be mechanistically linked and can be potential targets for treatment of estrogen receptor-positive breast cancer patients.