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

CERLIANI, JUAN PABLO; VANZULLI, SILVIA; PEREZ PIÑERO, CECILIA; BOTTINO, MARIA CECILIA; SAHORES, ANA; NUñEZ, MYRIAM; VARCHETTA, ROMINA; MARTINS, RUBEN; ZEITLIN, E.; HEWITT, SM; MOLINOLO, ALFREDO; LANARI, CLAUDIA; LAMB, CAROLINE A.

BREAST CANCER RESEARCH AND TREATMENT

SPRINGER

Año: 2011 p. 1 - 12

0167-6806

Fibroblast growth factor receptors (FGFR) are tyrosine kinase receptors which have been implicated in breast cancer. The goal 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 expression and/or localization of FGFR-2 and FGFR-3. In murine mammary carcinomas showing different degrees of hormone dependence, we found a progestin-induced increased expression, 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 FGFR-3 expression 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.