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

JUAN PABLO CERLIANI, PHD; SILVIA I VANZULLI, M.D., PHD ; CECILIA PÉREZ PINERO, PHD ; MARÍA C BOTTINO, PHD ; ANA SAHORES, M.S. ; MYRIAM NUÑEZ, PHD ; ROMINA VARCHETTA, M.D. ; RUBÉN MARTINS, M.D. ; EDUARDO ZEITLIN, M.D. ; STEPHEN M HEWITT, PHD ; ALFREDO A MOLINOLO, M.D., PHD ; CLAUDIA LANARI, PHD ; CAROLINE ANA LAMB, PHD

BREAST CANCER RESEARCH AND TREATMENT

SPRINGER

Año: 2012 vol. 133 p. 997 - 1008

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-ßestradiol induced changes in the expression and/or localization of FGFR-2 and FGFR3. 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