Open AccessAssociated expressions of FGFR-2 and FGFR-3: from mouse mammary gland physiology to human breast cancer
Author(s) -
Juan P. Cerliani,
Silvia I. Vanzulli,
Cecilia Pérez Piñero,
María Cecilia Bottino,
Ana Sahores,
Margarita Ostrowski de Núñez,
Romina Varchetta,
Rubén Martins,
Eduardo Zeitlin,
Stephen M. Hewitt,
Alfredo A. Molinolo,
Claudia Lanari,
Caroline A. Lamb
Publication year - 2011
Publication title -
breast cancer research and treatment
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.908
H-Index - 154
eISSN - 1573-7217
pISSN - 0167-6806
DOI - 10.1007/s10549-011-1883-6
Subject(s) - fibroblast growth factor receptor , breast cancer , mammary gland , immunohistochemistry , medicine , endocrinology , biology , estrogen receptor , cancer , receptor , cancer research , estrogen , fibroblast growth factor
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.